Composition for cushions, wound dressings and other skin-contacting products

ABSTRACT

A skin-contacting adhesive composition is described which has improved initial tack, long-term adhesion, water uptake and translucency characteristics and may be prepared by melt extrusion. Uses of these compositions are also described, for example, their use in wound dressings.

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority under 35 U.S.C. § 119(e)(1) toU.S. Provisional Application Serial No. 60/383,504 filed May 24, 2002.

FIELD OF THE INVENTION

[0002] This invention relates generally to skin-contacting adhesivecompositions, and more particularly relates to a novel compositionuseful in a variety of contexts including as a wound dressing, cushion,or the like that is applied to an individual's skin or other bodysurface.

BACKGROUND OF THE INVENTION

[0003] Various types of bandages and wound dressings are known and usedto protect wounds and bums. Typically, wound dressings are fabricatedwith an absorbent material so that wound exudate is removed and thewound dries, facilitating healing. Wound dressings may also contain oneor more pharmacologically active agents such as antibiotics, localanesthetics, or the like. Commonly used wound dressings include fibrousmaterials such as gauze and cotton pads, which are advantageous in thatthey are absorbent but problematic in that fibers may adhere to thewound or newly forming tissue, causing wound injury upon removal. Otherwound dressings have been prepared with foams and sponges, but theabsorbance of these materials is often limited. Furthermore, such wounddressings require the use of adhesive tape, as they are not themselvesadhesive. Finally, many of these wound dressings are not translucent ortransparent, thus rendering it difficult to monitor healing withoutremoval of the dressing.

[0004] To improve the absorbance of conventional fibrous wounddressings, water-swellable polymers or “hydrogels” have beenincorporated into gauze or other fibrous materials for application to awound. For example, U.S. Pat. No. 5,527,271 to Shah, et al. describes acomposite material made from a fibrous material, such as cotton gauze,impregnated with a thermoplastic hydrogel-forming copolymer containingboth hydrophilic and hydrophobic segments. While the wound dressings aredescribed as having increased absorptive capacity, the adhesion offibers to the wound or newly forming tissue remains a significantdisadvantage.

[0005] Another approach has been to use water-swellable polymericmaterials instead of gauze, cotton, and the like. Wound-contactingsurfaces made of such materials are not only more absorbent thanconventional fibrous materials, they are also advantageous in that thereis no risk of fiber adhesion during wound healing and upon removal ofthe wound dressing. Such wound dressings are disclosed, for example, inU.S. Pat. No. 4,867,748 to Samuelsen, which describes the use of anabsorbent wound-contacting composition made from a water-soluble orwater-swellable hydrocolloid blended with or dispersed in awater-insoluble, viscous, elastomeric binder. U.S. Pat. No. 4,231,369 toSorensen et al. describes “hydrocolloid plasters” as sealing materialsfor ostomy devices, the materials consisting of a continuous hydrophobicphase made from a hydrophobic pressure-sensitive adhesive, anelastomeric plasticizer, and a tackifying resin, with a discontinuousphase dispersed therein consisting of a water-soluble or water-swellablepolymer. Such plasters are also described in U.S. Pat. No. 5,643,187 toNaestoft et al. U.S. Pat. No. 6,201,164 to Wulff et al. describes asomewhat different type of hydrocolloid wound gel, consisting of awater-insoluble, water-swellable, crosslinked cellulose derivative, analginate, and water.

[0006] Hydrogel bandages have also been employed in wound dressings, asdescribed, for example, in U.S. Pat. No. 4,093,673 to Chang et al.Hydrogel bandages are made from a liquid absorbing crosslinked polymerand have a high water content prior to use. The high water contentcauses the hydrogel to exhibit very little or no adhesion, requiring theuse of adhesive tape or a plaster such as 2^(nd) Skin® dressingavailable from Spenco Medical Ltd., U.K.

[0007] However, in spite of the advances in the art, numerous problemscontinue to be encountered with gel-based wound dressings made withhydrocolloids and hydrogels. The reason for this is, in part, that thereare conflicting requirements for an ideal material. The material shouldnot be so adhesive that it tends to adhere to a wound and thus causepain or further injury upon removal. However a wound dressing shouldadhere sufficiently to a body surface so that separate adhesive tapesand adhesive plasters are not necessary. Peripheral adhesives can beused, but require an additional manufacturing step. In addition, a wounddressing should conform to the contours of the skin or other bodysurface, both during motion and at rest. For wound dressings that alsoserve as a cushioning pad, higher cohesive strength materials should beused, without any loss in adhesion.

[0008] Many of these problems can be solved by using a skin-contactingadhesive that also serves as a bandage or wound dressing. The idealskin-contacting adhesive would display very high swelling upon contactwith water, exhibit little or no cold flow during use, and could beeasily tailored during manufacture to optimize properties such asadhesive strength, cohesive strength, and hydrophilicity. It would alsobe desirable to be able to manufacture a skin-contacting adhesive usinga simple extrusion process, obviating the need for organic solvents andthe conventional, time-consuming blending and casting method.

[0009] Another desired goal, with respect to wound dressings, wouldenable a skin-contacting adhesive to be prepared that meets all of theforegoing criteria and is, in addition, translucent. With a translucentmaterial, it becomes possible to view the degree of wound healingthrough the dressing, in turn meaning that the dressing does not need tobe removed, changed, or partially peeled back from the skin in order toassess the degree of healing.

[0010] It would also be ideal if a skin-contacting adhesive met all ofthe above criteria and could also be adapted for uses other than woundhealing. Such uses might include, by way of example, fabrication oftransdermal drug delivery devices, preparation of medicated gels fortopical and transdermal pharmaceutical formulations, use inpressure-relieving cushions (which may or may not be medicated), use assealants for ostomy devices and prostheses, use as conductive adhesivesfor attachment of electroconductive articles such as electrodes to theskin, and the like.

[0011] The present invention addresses those needs by providing askin-contacting adhesive that meets all of the aforementioned criteria.

SUMMARY OF THE INVENTION

[0012] One aspect of the invention relates to a skin-contacting adhesive(SCA) composition comprised of a hydrophobic phase and a hydrophilicphase, where the hydrophobic phase comprises a hydrophobic polymer, atleast one elastomeric plasticizer and a tackifying resin; and thehydrophilic phase comprises at least one material selected from thegroup consisting of low molecular weight cellulose derived polymers andnaturally occurring polysaccharides, at least one high molecular weightcellulose derived polymer, and reinforcing clay particles.

[0013] Another aspect of the invention pertains to a skin-contactingadhesive composition comprised of a hydrophobic phase and a hydrophilicphase, where the hydrophobic phase comprises: a hydrophobic polymerselected from the group consisting of polyisobutylene, butyl rubbers,natural rubber adhesives, vinyl ether polymers, polysiloxanes,polyisoprene, styrene-isoprene-styrene block copolymers,styrene-butadiene-styrene block copolymers, isobutylene-isoprenecopolymers, butadiene acrylonitrile rubber, polychloroprene,ethylene-propylene-diene terpolymers, and combinations thereof; at leastone elastomeric plasticizer and a tackifying resin; and the hydrophilicphase comprises: at least one material selected from the groupconsisting of low molecular weight cellulose derived polymers andnaturally occurring polysaccharides, at least one high molecular weightcellulose derived polymer and reinforcing clay particles.

[0014] Still another aspect of the invention pertains to an adhesivecushion for application to the skin, comprising a skin-contacting layerof an adhesive composition comprised of a hydrophobic phase and ahydrophilic phase, where the hydrophobic phase comprises a hydrophobicpolymer, at least one elastomeric plasticizer and a tackifying resin;and the hydrophilic phase comprises at least one material selected fromthe group consisting of low molecular weight cellulose derived polymersand naturally occurring polysaccharides, at least one high molecularweight cellulose derived polymer and reinforcing clay particles; andlaminated thereto, a backing layer.

[0015] Yet another aspect of the invention relates to a wound dressingcomprising a laminated composite of a body facing layer having abody-contacting surface, and an outwardly facing non-occlusive backinglayer, wherein at least a portion of the body-contacting surface iscomprised of a skin-contacting adhesive comprised of a hydrophobic phaseand a hydrophilic phase, where the hydrophobic phase comprises ahydrophobic polymer, at least one elastomeric plasticizer and atackifying resin; and the hydrophilic phase comprises at least onematerial selected from the group consisting of low molecular weightcellulose derived polymers and naturally occurring polysaccharides, atleast one high molecular weight cellulose derived polymer andreinforcing clay particles.

[0016] Another aspect of the invention relates to a transdermal drugdelivery device comprised of a drug reservoir containing atherapeutically effective amount of an active agent, an outwardly facingbacking layer, and a means for affixing the device to a body surfacecomprising a skin-contacting adhesive composition, where the adhesivecomposition comprises a hydrophobic phase comprising a hydrophobicpolymer, at least one elastomeric plasticizer and a tackifying resin;and a hydrophilic phase comprising at least one material selected fromthe group consisting of low molecular weight cellulose derived polymersand naturally occurring polysaccharides, at least one high molecularweight cellulose derived polymer and reinforcing clay particles.

[0017] Still another aspect of the invention relates to a transdermaldrug delivery device comprised of a drug reservoir containing atherapeutically effective amount of an active agent and an outwardlyfacing backing layer, wherein the drug reservoir is comprised of askin-contacting adhesive composition, wherein the adhesive compositioncomprises a hydrophobic phase comprising a hydrophobic polymer, at leastone elastomeric plasticizer and a tackifying resin; and a hydrophilicphase comprising at least one material selected from the groupconsisting of low molecular weight cellulose derived polymers andnaturally occurring polysaccharides, at least one high molecular weightcellulose derived polymer and reinforcing clay particles.

[0018] Yet another aspect of the invention relates to a skin-contactingadhesive composition comprised of a hydrophobic phase and a hydrophilicphase, wherein the hydrophilic phase has a fiber-particle morphology.The hydrophilic phase is made of: fibers of a liquid crystalline highmolecular weight cellulose derived polymer; ordered particles of clay;and randomly distributed spherical solid droplets of a low molecularweight cellulose derived polymer, naturally occurring polysaccharide, orcombination thereof.

BRIEF DESCRIPTION OF THE DRAWING

[0019]FIG. 1 illustrates the morphology of the skin-contacting adhesiveof the invention.

[0020]FIG. 2 is a punch suitable for processing the adhesives, cushionsand wound dressings of the invention.

[0021]FIG. 3 is a rheokinetic curve for the precursor for formulation 17and the complete formulation 17 of Example 7.

[0022]FIG. 4 presents the results of squeeze-recoil tests conducted onformulation 17 of Example 7.

DETAILED DESCRIPTION OF THE INVENTION

[0023] The present invention is a skin-contacting adhesive that findsutility in numerous applications. In particular, due to theskin-contacting adhesive (SCA) properties under moist and load-bearingconditions, it finds particular utility for medical films used in footcare. For example, the adhesive can be applied to the sole of the foot,to the toes or to any other location on the foot to treat pain caused bya callus, corn, bunion, or blister, by providing a cushion effect. Theskin-contacting adhesive composition is comprised of a hydrophobic phaseand a hydrophilic phase. The hydrophobic phase includes a hydrophobicpolymer, at least one elastomeric plasticizer and a tackifying resin.The hydrophilic phase includes at least one low molecular weightcellulose derived polymer or naturally occurring polysaccharide, or acombination thereof. The hydrophilic phase also includes at least onehigh molecular weight cellulose derived polymer and reinforcing clayparticles.

[0024] The skin-contacting adhesive of the invention provides forprolonged hydrations such that it is able to absorb water found in theenvironment or from the body surface to which it is applied. Inparticular, it is preferred that the adhesive remain translucent uponwater uptake over a typical wearing time of 72 hours. Theskin-contacting adhesive has rapid initial tack in that it grabs quicklyto the skin surface during application, is pressure and body sensitiveand able to maintain excellent adhesion while subjected to load bearingforces, such as those experienced when the adhesive is positioned on alower foot surface. In addition, the skin-contacting adhesive ispreferably skin and user friendly for at least 72 hours of continuouswear.

[0025] The hydrophilic phase of the skin-contacting adhesive of theinvention also has a unique fiber-particle morphology, where the highmolecular weight cellulose derived polymer (as a liquid crystal) ispresent as fibers, the clay component is present as ordered particles,and the low molecular weight cellulose derived polymer and/or naturallyoccurring polysaccharide is present as randomly distributed sphericalsolid droplets.

[0026] The aforementioned characteristics are readily achieved bycareful selection of the individual components in the adhesivecomposition, as well as adjusting one or more parameters duringfabrication.

[0027] Before describing the detailed embodiments of the invention, itwill be useful to set forth definitions that are used in describing theinvention. The definitions set forth apply only to the terms as they areused in this patent and may not be applicable to the same terms as usedelsewhere, for example in scientific literature or other patents orapplications including other applications by these inventors or assignedto common owners. Additionally, when examples are given, they areintended to be exemplary only and not to be restrictive and it isfurther to be understood that unless otherwise indicated this inventionis not limited to specific materials, active agents, additives, and soforth, as such may vary. For example, when an example is said to“include” a specific feature, that is intended to imply that it may havethat feature but not that such examples are limited to those thatinclude that feature. Thus, for example, reference to “a cellulosederived polymer” includes a mixture of two or more such polymers, and soforth. Finally, it must be noted that, as used in this specification andthe appended claims, the singular forms “a,” “an” and “the” includeplural referents unless the context clearly dictates otherwise. Thus,for example, reference to “an active agent” includes a mixture of two ormore such agents, and the like.

[0028] I. DEFINITIONS

[0029] In describing and claiming the present invention, the followingterminology will be used in accordance with the definitions set outbelow.

[0030] The terms “hydrophobic polymer” and “hydrophilic polymer” areintended to be defined relative to the amount of water vapor absorbed bypolymers at 100% relative humidity. According to this classification,hydrophobic polymers absorb only up to 1 wt % of water at 100% relativehumidity (rh), while moderately hydrophilic polymers absorb 1-10 wt % ofwater, hydrophilic polymers are capable of absorbing more than 10 wt %of water, and hygroscopic polymers absorb more than 20 wt % of water.

[0031] The terms “tack” and “tacky” are qualitative. However, the terms“substantially nontacky”, “slightly tacky” and “tacky,” as used herein,may be quantified using the values obtained by a PSA TackDetermination/Polyken Probe method (Solutia, Inc.). By “substantiallynontacky” is meant an adhesive that has a tack value that is less thanabout 25 g-cm/sec, by “slightly tacky” is meant an adhesive that has atack value in the range of about 25 g-cm/sec to about 100 g-cm/sec, andby “tack” is meant an adhesive that has a tack value of at least 100g-cm/sec.

[0032] The term “translucent” is used to signify a material capable oftransmitting light so that objects or images can be seen through thematerial. Translucent materials herein may or may not be “transparent,”meaning that the material is optically clear. The term “translucent”indicates that a material is not “opaque,” in which case objects andimages either cannot be seen through the material.

[0033] The term “active agent” refers to a chemical material or compoundsuitable for topical or transdermal administration and that induces adesired effect. The terms include agents that are therapeuticallyeffective, prophylactically effective, and cosmetically effectiveagents. Also included are pharmaceutically acceptable, pharmacologicallyactive derivatives of those active agents specifically mentioned herein,including, but not limited to, salts, esters, amides, prodrugs, activemetabolites, inclusion complexes, analogs, and the like, which alsoinduce the desired effect. The terms “active agent”, “drug” and“therapeutic agent” are used interchangeably herein.

[0034] By “transdermal” delivery is meant administration of an activeagent to the skin surface of an individual so that the agent passesthrough the skin tissue and into the individual's blood stream. The term“transdermal” is intended to include transmucosal administration, i.e.,administration of a drug to the mucosal (e.g., sublingual, buccal,vaginal, rectal) surface of an individual so that the agent passesthrough the mucosal tissue and into the individual's blood stream.

[0035] The term “body surface” is used to refer to skin or mucosaltissue, including the interior surface of body cavities that have amucosal lining. The term “skin” should be interpreted as including“mucosal tissue” and vice versa.

[0036] The term “therapeutically effective amount” is intended to meanthe amount of an active agent that is nontoxic but sufficient to providethe desired effect. The amount that is “effective” will vary fromsubject to subject, depending on the age and general condition of theindividual, the particular active agent or agents, and the like. Thus,it is not always possible to specify an exact effective amount. However,an appropriate effective amount in any individual case may be determinedby one of ordinary skill in the art using routine experimentation.Furthermore, the exact effective amount of an active agent incorporatedinto the adhesive of the invention is not critical, so long as theconcentration is within a range sufficient to permit ready applicationof the formulation so as to deliver an amount of the active agent thatis within a therapeutically effective range.

[0037] II. COMPOSITIONS

[0038] The desirable adhesive characteristics are achieved by selectionof the individual components as well as adjusting one or more parametersduring fabrication. For example, the adhesive strength of the adhesivecan be controlled during manufacture in order to increase, decrease, oreliminate adhesion. This can be accomplished by varying the type and/oramount of different adhesive components, or by changing the mode offabrication. For example, incorporating greater amounts of theelastomeric plasticizer and the tackifying resin in the hydrophobicphase will increase tack, while reducing the amounts of those componentsor incorporating detackifier additives or increasing the level ofpowdered hydrophilic components, will decrease tack. Also, with respectto the fabrication process, adhesives prepared using a conventional meltextrusion process tend to be more tacky, while adhesives prepared by amolding procedure tend to have lower tack. In addition, adhesives may berendered translucent by changing the relative quantities of thecomponents in the hydrophilic phase (e.g., by decreasing the amount ofclay, the cellulose derived polymer or natural polysaccharides), or bychanging the conditions (temperature, extrusion rate, thickness, etc.)of fabrication method. Furthermore, the degree to which the adhesivewill swell upon contact with water can be varied by selecting differentwater-swellable and water-soluble hydrophilic polymers and their ratio.Combination of water-swellable and water-soluble hydrophilic polymersallows us to control the swelling degree of SCA and to create acapability of SCA for re-application after their additional wetting.

[0039] The skin-contacting adhesive composition of the invention iscomprised of a hydrophobic phase and a hydrophilic phase. Typically, thecomposition will be about 50-80 wt % hydrophobic phase and about 20-50wt % hydrophilic phase. One preferred embodiment has about 60-70 wt %hydrophobic phase and about 30-40 wt % hydrophilic phase.

[0040] The hydrophobic phase comprises a hydrophobic polymer, at leastone elastomeric plasticizer and a tackifying resin, while thehydrophilic phase comprises at least one material selected from thegroup consisting of low molecular weight cellulose derived polymers andnaturally occurring polysaccharides, at least one high molecular weightcellulose derived polymer and reinforcing clay particles. A typicalcomposition is described below. Preferred More Preferred Ingredient Wt %range Wt % range Hydrophobic polymers 10-50  15-46  Elastomericplasticizers 5-40 5-31 Tackifying resin 0.5-40   1-35 High MW cellulosederived polymers 5-40 5-32 Low MW cellulose derived polymers 1-20 3-17(when present) Naturally occurring polysaccharides (when 2-40 5-20present) Clay particles 2-30 3-20 Optional ingredients 0-20 0.1-10  

[0041] As noted in the table, when a low MW cellulose derived polymer isincluded, the naturally occurring polysaccharide can be omitted and viceversa. Thus the invention includes compositions having only a low MWcellulose derived polymer, having only a naturally occurringpolysaccharide or having both.

[0042] For those embodiments of the invention, where the hydrophilicphase comprises only low and high molecular weight cellulose derivedpolymers, i.e., no naturally occurring polysaccharides, a typicalcomposition is described below. Preferred More Preferred Ingredient Wt %range Wt % range High and Low MW Cellulose derived 12-60 18-45 polymersClay particles  2-10 3-6

[0043] Higher amounts of clay can be included in those embodiments wherethe hydrophilic phase includes at least one naturally occurringpolysaccharide, alone or in combination with one or more low molecularweight cellulose derived polymers. A typical composition is describedbelow. Preferred More Preferred Ingredient Wt % range Wt % rangeNaturally occurring polysaccharides 2-40 5-30 Clay particles 2-30 4-20

[0044] Exemplary composition are set forth below and in the Examples.The skin-contacting adhesive (SCA) finds utility in wound dressings, forexample. The formulation of Cushions 1 and 2 lend themselves to cushionsthat will be load-bearing, for example to treat a callus under the foot,while the formulation of Cushion 3 is more suited to treat corns,blisters and bunions that are present on the top or sides of the foot.Weight Percent Ingredient SCA Cushion 1 Cushion 2 Cushion 3 Hydrophobicpolymer 19.0 20.0 20.0 20.0 Elastomeric plasticizer 14.5 15.0 15.0 19.0Tackifying resin 28.0 25.5 25.5 25.5 High MW cellulose derived 22.0 15.010.0 10.0 polymer Low MW cellulose derived 12.0 — 3.0 8.5 polymerNaturally occurring polysac- — 15.0 17.0 10.0 charide Clay particles 3.08.0 8.0 4.0 Optional ingredients 1.5 1.5 1.5 3.0

[0045] In the aforementioned skin-contacting adhesive and cushionformulations, an exemplary formulation utilizes astyrene-isoprene-styrene block copolymer, alone or in combination with astyrene-isoprene block copolymer, as the hydrophobic polymer; a lowmolecular weight polyisoprene rubber as the elastomeric plasticizer; anon-polar tackifying resin as the tackifying resin;hydroxypropylcellulose as the high and low MW cellulose derivedpolymers; and agar as the naturally occurring polysaccharide. Othermaterials that are also well suited for use in the invention, aredescribed in detail below. In addition, a preferred embodiment includesa polyisobutylene adhesive material as the optional ingredient.

[0046] These percentages are intended to merely be illustrative of thecompositions of the invention. There are other factors that can be takeninto consideration when ascertaining the actual materials and quantitiesto be used in the formulations. For example, the weight ratios ofcertain materials can be selected so as to optimize the adhesivestrength, cohesive strength and water sorbtion of the composition. Theseinclude the weight ratio of the hydrophobic phase and the hydrophilicphase; the weight ratio of the high MW cellulose derived polymers, lowMW cellulose derived polymers or naturally occurring polysaccharides,and the reinforcing clay particles; and the weight ratio of thehydrophobic polymer, elastomeric plasticizer and tackifying resin.

[0047] Similarly, the weight ratios of these same materials can beselected so as to render the composition translucent, which is adesirable characteristic for some applications of the adhesive.Interestingly, the hydrophilic phase maintains its translucentcharacteristics in spite of its heterogeneous characteristic, i.e., thehigh molecular weigh cellulose derived polymers, as well as low MWcellulose derived polymers (when included) are in a melt phase and theclay particles, as well as the naturally occurring polysaccharides (whenincluded) are in the dispersed phase.

[0048] A sketch of morphology of the hydrophobic phase of the SCA of theinvention is shown in FIG. 1. This is intended to be illustrative andnot limiting. The exemplary SCA has a backing layer 1 and a removablerelease liner 2. The hydrophobic phase 3 has a high molecular weightcellulose derivative 5 as well as clay particles 7. The hydrophobicphase further comprises a low Mw cellulose derivative 4 and/or anaturally occurring polysaccharide 6.

[0049] A. Hydrophobic Phase-Hydrophobic Polymer

[0050] Suitable hydrophobic polymers include, by way of illustration andnot limitation, polyisobutylenes, butyl rubbers, natural rubberadhesives, vinyl ether polymers, polysiloxanes, polyisoprenes,styrene-isoprene-styrene block copolymers, styrene-butadiene-styreneblock copolymers, isobutylene-isoprene copolymers, butadieneacrylonitrile rubber, polychloroprenes, ethylene-propylene-dieneterpolymers, and combinations thereof. Styrene-isoprene-styrene blockcopolymers, styrene-butadiene-styrene block copolymers and butyl rubbersare particularly well suited for use in the invention.

[0051] In one embodiment of the invention, the hydrophobic polymer is atriblock styrenic copolymer such as styrene-isoprene-styrene (SIS) orstyrene-butadiene-styrene (SBS) and can further comprises the diblockcopolymer, styrene-isoprene (SI) block copolymer. Such mixtures cancontain up to 45 wt % of the SI diblock copolymer.

[0052] Commercially available styrene-based block copolymers such as theVector series (available from Dexco Polymers) are particularly useful inthe invention. These include the SIS Vector 4111 (18 wt % styrene/82 wt% isoprene) and 4411 (44 wt % styrene/56 wt % isoprene) as well asSIS/SI mixtures such as Vector 4113 (18 wt % SI diblock; overall 15 w t% styrene/85 wt % isoprene), Vector 4114 (42 wt % SI diblock; overall 15wt % styrene/85 wt % isoprene), Vector 4213 (25 wt % SI diblock; overall25 wt % styrene/75 wt % isoprene) and Vector 4215 (18 wt % SI diblock;overall 30 wt % styrene/70 wt % isoprene).

[0053] In another embodiment of the invention, the hydrophobic polymeris a polyisoprene or a butyl rubber. Commercially availablepolyisoprenes such as the high molecular weight polyisoprene rubberNatsyn® 2210 (Goodyear Tire and Rubber), and butyl rubbers such as thehigh molecular weight butyl rubber BR 065 (Exxon), are particularlyuseful in the invention.

[0054] Accordingly, in one embodiment of the invention, theskin-contacting adhesive composition comprises of a hydrophobic phaseand a hydrophilic phase, where the hydrophobic phase comprises ahydrophobic polymer selected from the group consisting ofpolyisobutylene, butyl rubbers, natural rubber adhesives, vinyl etherpolymers, polysiloxanes, polyisoprene, styrene-isoprene-styrene blockcopolymers, styrene-butadiene-styrene block copolymers,isobutylene-isoprene copolymers, butadiene acrylonitrile rubber,polychloroprene, ethylene-propylene-diene terpolymers, and combinationsthereof. The hydrophobic phase also contains at least one elastomericplasticizer and a tackifying resin, while the hydrophilic phasecomprises the low molecular weight cellulose derived polymer ornaturally occurring polysaccharide, the high molecular weight cellulosederived polymers and the reinforcing clay particles.

[0055] In the case of unsaturated rubbers a curing agent may be added tofix the SCA structure and to prevent cold flow. Since it is desirable toreach the specific rheological properties of SCA, namely diminished coldflow, i.e., substantially total elastic recovery, unsaturatedhydrophobic components (butyl rubber, natural rubber, syntheticpolyisoprene rubber, etc.) are preferably crosslinked. Polymerscontaining double bonds undergo a process of chemical crosslinking withformation of covalent bonds. The density of the resultant chemicalnetwork should not be too high, in order to preserve the desired tack.The number of crosslinks in the volume unit can be controlled by thenature and amount of crosslinkers, as well as by the temperature-timeprocedure followed. Phenolformaldehyde resins andalkylphenolformaldehyde resins are suitable crosslinkers for butylrubber, while dicumyl peroxide can be used for polyisoprenes.

[0056] The most convenient method of monitoring the degree ofcrosslinking involves measurement of the change in melt viscosity overtime. The resulting rheokinetic curve demonstrates the rate ofcrosslinking and the plateau region corresponds to the completion of thechemical interaction of double bonds of unsaturated hydrophobic polymerswith the crosslinkers. This rheokinetic curve is shown, for example, inFIG. 3.

[0057] In the case of triblock-copolymers, e.g. SIS or SBS, theirsolidification occurs as they cool due to the segregation of styreneblocks and their transition to glassy state. At ambient temperature theelastic recoil of triblock-copolymers formulations, exceeds 90%. Thepresence of elastomeric isoprene or butadiene blocks in themacromolecules of SIS and SBS, as well as the additional components ofthe hydrophobic phase (e.g., plasticizers), results in the desired tackand adhesive properties.

[0058] B. Hydrophobic Phase-Elastomeric Plasticizer

[0059] The elastomeric plasticizer is preferably selected so as to becompatible with triblock-copolymers, i.e., forms a solution withmultiblock-copolymers inside the definite temperature-concentrationregion of the phase diagram. Thus, one of skill in the art can readilyuse phase diagrams of the hydrophobic phase components for guidanceconcerning the appropriate amounts of each component to use.

[0060] Suitable elastomeric plasticizers include block polymers having a“multiarmed (AB)_(x)” configuration, where for example, A is apolymerized block comprising aryl-substituted vinyl monomers, preferablystyrene, α-methyl styrene, vinyl toluene, and the like, B is anelastomeric, conjugated polybutadiene or polyisoprene block, and x has avalue of 3 or more. Preferred plasticizers are styrene-based polymers,particularly styrene-butadiene block copolymers and styrene-isopreneblock copolymers, and combinations thereof. Many of these are readilyavailable commercially, such as the styrene-isoprene block copolymersold under the name LVSI 101 (Kraton).

[0061] The elastomeric plasticizer can also be a low molecular weightpolyisobutylene, or a low molecular weight polyisoprene rubber(MW=20,000-100,000) such as cis-1,4 polyisoprene (e.g., Isolene® 400 orIsolene 40 from Elementis Performance Polymers), optionally mixed withparaffin oil.

[0062] In one embodiment of the invention, the hydrophobicphase-elastomeric plasticizer includes both a block polymer (e.g.,styrene) and a low molecular weight polyisoprene rubber (e.g. cis-1,4polyisoprene).

[0063] C. Hydrophobic Phase-Tackifying Resin

[0064] The tackifying resin is a relatively low molecular weight resin(weight average molecular weight generally less than about 50,000)having a fairly high glass transition temperature. Its function is toincrease the strength of adhesion bonds. Tackifying resins include, forexample, rosin derivatives, terpene resins, and synthetic or naturallyderived petroleum resins. Preferred tackifying resins herein aregenerally non-polar tackifying resins selected from the group consistingof hydrogenated hydrocarbon resins, hydrocarbon resins and syntheticpolyterpene resins. The tackifying resin is preferably miscible withhydrophobic polymer/plasticizer composition to provide a ternarysolution. Commercially available resins within these classes includeRegalrez 1085 (hydrogenated hydrocarbon resin) and Regalite Resins suchas Regalite 9100 (partially hydrogenated hydrocarbon resin, availablefrom Hercules); Escorez 1304 and Escorez 1102 (hydrocarbon resins), andEscorez 5380 (cyclicaliphatic hydrocarbon resin) available from ExxonChemical Company, Wingtack 95 and Wingtack 85 (synthetic polyterpeneresins), available from Goodyear Tire and Rubber.

[0065] D. Hydrophilic Phase-Low and High MW Cellulose Derived Polymers

[0066] The cellulose derived polymers useful in the skin-contactingadhesive of the invention are preferably water-swellable orwater-soluble hydrophilic polymers. The term “high” molecular weight(MW) refers to those cellulose derived polymers having a molecularweight within the range of about 300-1,150 kg/mole, more typicallywithin the range of about 350-850 kg/mole. The term “low” molecularweight (MW) refers to those cellulose derived polymers having amolecular weight within the range of about 80-140 kg/mole.

[0067] Several water-soluble cellulose derivatives can be melted andintroduced to the formulation by mixing through the melt state. Thisfeature leads to possibility to control the morphology of hydrophilicpart of SCA. Depending upon the molecular weight of the cellulosederived polymer, it can form either spherical droplets or long liquidjets at mixing, transforming to solid fibers upon cooling.

[0068] Suitable water-soluble cellulose derived polymers includehydroxypropylcellulose (HPC) of different MW. HPC melts at ˜120-130° C.and forms long fibers upon agitation, which then penetrate theformulation. Since HPC melts are liquid-crystalline, i.e., the HPCchains are packed with a definite correlation of long axis, givingso-called nematic or cholesteric structure, the capability to change theshape of the droplets at deformation (“strain susceptibility”) at mixingis higher than for isotropic polymer melts. For that reason, HPCpolymers readily form long liquid threads that, upon cooling, providesfor long solid fibers having excellent molecular orientation along thelong axis of fibers. These fibers serve as channels for fast moisturestransportation from the wound/skin to the depth of SCA.

[0069] Thus, the combination of HPC of different molecular weightprovides for the creation of a droplet/fiber morphology of thehydrophilic phase of the SCA, which provides rapid moisture penetrationand high water uptake during use.

[0070] The HPC-water phase diagram contains three different phase statesat T<43° C., as the HPC content increases: up to 35% HPC,liquid-crystalline solution (up to 80% HPC, and crystalhydrate (additivecompound of one mole of HPC and six moles of water). At T>43° C. thecrystalhydrate decomposes to HPC and free water. The rate of polymerinteraction with water can be expressed by the interdiffusioncoefficient onto interface, D_(v), determined by optical interference.Its values for different systems (including PVP as a reference) arepresented below. Polymer D_(v)10¹¹, m²/c PVP (MW = 10⁶) 4.0 Na—CMC (type7 LF) 2.0 HPC (MW = 80,000) 1.8 HPC (MW = 140,000) 1.7 HPC (MW =370,000) 1.5 HPC (MW = 850,000) 1.3 HPC (MW = 1,150,000) 1.2

[0071] PVP interacts with water very quickly, but this leads tosoftening SCA as whole. HPC's and Na-CMC have comparable interdiffusioncoefficients, but HPC is able to form a swelled (gel-like) layer, whichcan reduce (or control) the further penetration of water into thepolymer. In addition, a combination of different grades of HPC allowsfor regulating the rate of moisture penetration. In a preferredembodiment, the weight ratio of low MW to high MW cellulose derivedpolymer is about 1:1 to 1:2.

[0072] Suitable cellulose derived polymers include, but are not limitedto, hydratecellulose (cellophane), hydroxypropylcellulose (HPC),hydroxypropylmethylcellulose (HPMC), and sodium carboxymethylcellulose(Na-CMC).

[0073] There are numerous commercially available cellulose derivedpolymers that can be used in the adhesive of the invention. For example,EF (molecular weight of 80 kg/mole), LF (molecular weight of 80-95kg/mole), JF (molecular weight of 140 kg/mole), GF (molecular weight of370 kg/mole), MF (molecular weight of 850 kg/mole) and HF (molecularweight of 1,150 kg/mole) are various grades of HPC polymers availableunder the tradename Klucel® (Hercules Inc.).

[0074] E. Hydrophilic Phase-Naturally Occurring Polysaccharides

[0075] Naturally occurring polysaccharides include materials such asagars of various origin; alginates including alginic acid, salts ofalginic acid (e.g., calcium alginate, potassium alginate, sodiumalginate), and derivatives of alginic acid (e.g. propylene glycolalginate, Kelcoloid®, Monsanto); carrageenans including kappa-, iota-and lambda carrageenans; chitin; chitosan; glucomannan; gum guar (TICGums); gellan gum (Kelcogel®, Monsanto); locust bean gum; pectins suchas pectin and amylopectin; pullulan; starches (e.g., potato starchacetate, Clearam® CH10, Roquette); xanthans such as xanthane gum; andcombinations thereof.

[0076] Particularly preferred naturally occurring polysaccharidesinclude, by way of illustration and not limitation, agar, gum guar,gellan gum, calcium alginate, starches, and so forth. The polysaccharidemay be charged, and thus able to interact with the clay particles.Typically, the polysaccharides are water-swellable at room temperaturewith very high water uptake. Some may also dissolve in boiling water andform a gel at cooling. The polysaccharides provides for enhancedaccumulation and storage of moisture in the SCA.

[0077] In a preferred embodiment, the weight ratio of naturallyoccurring polysaccharide to cellulose derived polymer is about 1:1 to2:1.

[0078] F. Hydrophilic Phase-Reinforcing Clay Particles

[0079] The clay particles used in the skin-contacting adhesive of theinvention are responsible for many of the beneficial aspects of theinvention. For example, the clay particles: help to provide a wickingaction to remove moisture from the skin surface and store it; reinforcethe yield behavior that prevents the cold flow; help the compositionmaintain its adhesive nature as well as providing structural support tosupply the high elastic recoil at application of SCA on the sole offoot, etc.

[0080] In general, clay materials are typically plastic when moist buthard when heated, and are often composed mainly of fine particles ofhydrous aluminum silicates, alone or in combination with other minerals.In particular, suitable clay particle materials are selected from thegroup consisting of phyllosilicates (layered silicates) and layereddouble hydroxides (minerals and synthetic materials with positivelycharged brucite-type layers of mixed metal hydroxides). Such materialsare described in detail in references such as “Polymer-ClayNanocomposites”, ed. T. J. Pinnavaia and G.W. Beall (Wiley Series inPolymer Science, John Wiley & Sons, Ltd., ©2000), the disclosure ofwhich is incorporated herein by reference.

[0081] In one embodiment of the invention, the phyllosilicate isselected from the group consisting of allophane (hydrated aluminumsilicate); apophyllite (hydrated potassium sodium calcium silicatehydroxide fluoride); bannisterite (hydrated potassium calcium manganeseiron zinc aluminum silicate hydroxide); carletonite (hydrated potassiumsodium calcium silicate carbonate hydroxide fluoride); cavansite(hydrated calcium vanadate silicate); chrysocolla (hydrated copperaluminum hydrogen silicate hydroxide); clay minerals (described indetail below); delhayelite (hydrated sodium potassium calcium aluminumsilicate chloride fluoride sulfate); elpidite (hydrated sodium zirconiumsilicate); fedorite (hydrated potassium sodium calcium silicatehydroxide fluoride); franklinfumaceite (calcium iron aluminum manganesezinc silicate hydroxide); franklinphilite (hydrated potassium manganesealuminum silicate); gonyerite (manganese magnesium iron silicatehydroxide); gyrolite (hydrated calcium silicate hydroxide); kanemite;kenyaite; leucosphenite (hydrated barium sodium titanium boro-silicate);magadiite; makatite; micas such as biotite (potassium iron magnesiumaluminum silicate hydroxide fluoride), lepidolite (potassium lithiumaluminum silicate hydroxide fluoride), muscovite (potassium aluminumsilicate hydroxide fluoride), paragonite (sodium aluminum silicatehydroxide), phlogopite (potassium magnesium aluminum silicate hydroxidefluoride) and zinnwaldite (potassium lithium aluminum silicate hydroxidefluoride); minehillite (hydrated potassium sodium calcium zinc aluminumsilicate hydroxide); nordite (cerium lanthanum strontium calcium sodiummanganese zinc magnesium silicate); octosilicate; pentagonite (hydratedcalcium vanadate silicate); petalite (lithium aluminum silicate);prehnite (calcium aluminum silicate hydroxide); rhodesite (hydratedcalcium sodium potassium silicate); sanbomite (barium silicate);serpentines such as antigorite (magnesium iron silicate hydroxide),clinochrysotile (magnesium silicate hydroxide), lizardite (magnesiumsilicate hydroxide), orthochrysotile (magnesium silicate hydroxide) andserpentine (iron magnesium silicate hydroxide); wickenburgite (hydratedlead calcium aluminum silicate); and zeophyllite (hydrated calciumsilicate hydroxide fluoride).

[0082] In one preferred embodiment, the clay material is aphyllosilicate selected from the group consisting of clay minerals,kanemite, kenyaite, magadiite and makatite.

[0083] In another preferred embodiment, the phyllosilicate is a claymineral, which is a group of phyllosilicates that contain a largepercentage of water trapped between the silicate sheets. Most clayminerals are chemically and structurally analogous to otherphyllosilicates but the larger amounts of water present, allow for moresubstitution of their cations.

[0084] Suitable clay minerals include chlorites such as baileychlore(zinc iron aluminum magnesium silicate hydroxide), chamosite (ironmagnesium aluminum silicate hydroxide oxide), the generallized mineralchlorite, clinochlore (a chromium variety kaemmererite) (iron magnesiumaluminum silicate hydroxide), cookeite (lithium aluminum silicatehydroxide), nimite (nickel magnesium iron aluminum silicate hydroxide),pennantite (manganese aluminum silicate hydroxide), penninite (ironmagnesium aluminum silicate hydroxide) and sudoite (magnesium aluminumiron silicate hydroxide); glauconite (potassium sodium iron aluminummagnesium silicate hydroxide); illite (hydrated potassium aluminummagnesium iron silicate hydroxide); kaolinite (aluminum silicatehydroxide); montmorillonite (hydrated sodium calcium aluminum magnesiumsilicate hydroxide); palygorskite (hydrated magnesium aluminum silicatehydroxide); pyrophyllite (aluminum silicate hydroxide); sauconite(hydrated sodium zinc aluminum silicate hydroxide); talc (magnesiumsilicate hydroxide); and vermiculite (hydrated magnesium iron aluminumsilicate hydroxide).

[0085] Swellable clay minerals are those that have alkali metals betweentheir layers and can swell in polar solvents. These include lithiumcontaining materials such as cookeite; sodium containing materials suchas glauconite (which also contains potassium), montmorillonite andsauconite; and potassium containing materials such as illite. In someinstances, such swellable materials are preferred over the non-swellableclay minerals.

[0086] It may be desirable to treat the phyllosilicate particles with anorganic material to intercalate organic molecules between adjacent,planar silicate layers. For example, treatment can be with an organicmaterial such as silane coupling agents; quaternary ammonium compounds;monomeric compounds having an electrostatic functionality selected fromthe group consisting of amines, amides and mixtures thereof; monomericcompounds having a functionality selected from the group consisting ofhydroxyl, aromatic rings, carbonyl, carboxylic acid, polycarboxylicacid, aldehydes, ketones, amines, amides, ethers, esters andcombinations thereof; an N-alkenyl amide monomer/allylic monomercombination, an oligomer formed by copolymerizing an N-alkenyl amidemonomer and an allylic monomer, a polymer formed by copolymerizing anN-alkenyl amide monomer and an allylic monomer, and mixtures thereof, anintercalant polymer; and so forth.

[0087] In spite of some hydrophobization of the particle surface, such atreatment, for example by dioctadecyl ammonium chloride, leads todistinctive separation of clay platelets and their homogeneousdistribution in polymer matrix. The reinforcing clay particles typicallyhave an average diameter of about <15μ, and the average diameter ispreferably within the range of about 2-6μ. Their thickness is around10-100 nanometers and therefor can be referred to as nanoparticles, andthe SCA is thus a “nanocomposite”. Preferred clay particles aremontmorillonite particles and are available from Southern Clay ProductsCo under the trademarks Cloisite Na+ (interspace length is 11.7),Cloisite 15A (interspace length is 31.5, clay modified withdioctylammoniumchloride to render it more hydrophobic), Cloisite 20A,and so forth.

[0088] G. Optional Additives

[0089] The adhesive may also include conventional additives such asadhesive agents, antioxidants, crosslinking or curing agents, pHregulators, pigments, dyes, refractive particles, conductive species,antimicrobial agents, active agents and permeation enhancers. In thoseembodiments wherein adhesion is to be reduced or eliminated,conventional detackifying agents may also be used. These additives, andamounts thereof, are selected in such a way that they do notsignificantly interfere with the desired chemical and physicalproperties of the adhesive.

Adhesive Agents

[0090] The skin-contacting adhesive of the invention can also includeadditional adhesive agents that serve to improve the adhesive and tackproperties of the adhesive, which is particularly beneficial to maintainadhesiveness when the skin-contacting adhesive is used in a manner suchthat it is subjected to a large amount of mechanical stress. Exemplarymaterials include tacky rubbers such as polyisobutylene, polybutadiene,butyl rubber, polystyrene-isoprene copolymers, polystyrene-butadienecopolymers, and neoprene (polychloroprene). Preferred adhesive agentsinclude low molecular weight polyisobutylene and butyl rubber.

[0091] In one embodiment, the hydrophobic pressure-sensitive adhesivematerial is added to the hydrophobic phase materials. A hydrophobicpressure-sensitive adhesive material such as PIB tends to have a lowsurface energy (30.5 mJ/m²) compared with SIS (35.0 mJ/m²) and the freshSCA (32.5 mJ/m²). Therefore, the PIB can readily migrate onto the patchsurface. This migration can be accelerated by heating the patch, forexample at 50° C. for 2 hours. After this treatment, the surface energyof formulation becomes equal to 30.7 mJ/m², i.e., close to PIB surfaceenergy. Therefore, the inclusion of PIB in the contact zone with skinincreases the initial tack.

[0092] A similar effect can be achieved by coating the patch surfacewith a dilute PIB solution in chloroform. After evaporation of solvent,the thin PIB layer forms reinforcing the initial tack without initiationof additional cold flow. Accordingly, the invention also contemplatescoating the hydrophobic pressure-sensitive adhesive material onto thesystem and then heating the coating to remove any solvent and enable thematerial to diffuse into the system.

Antioxidants

[0093] The skin-contacting adhesive of the invention may also includeone or more antioxidants. If used, the antioxidant is typicallyincorporated into the hydrophobic phase, and serves to enhance theoxidative stability of the composition. Heat, light, impurities, andother factors can all result in oxidation of the adhesive. Thus,ideally, antioxidants should protect against light-induced oxidation,chemically induced oxidation, and thermally induced oxidativedegradation during processing and/or storage. Oxidative degradation, aswill be appreciated by those in the art, involves generation of peroxyradicals, which in turn react with organic materials to formhydroperoxides. Primary antioxidants are peroxy free radical scavengers,while secondary antioxidants induce decomposition of hydroperoxides, andthus protect a material from degradation by hydroperoxides. Most primaryantioxidants are sterically hindered phenols, and exemplary compoundsfor use herein are tetrakis [methylene(3,5-di-tert-butyl-4-hydroxyhydrocinnamate)] methane (e.g.,Irganox®1010, from Ciba-Geigy Corp., Hawthorne, N.Y.) and1,3,5-trimethyl-2,4,6-tris [3,5-di-t-butyl-4-hydroxy-benzyl] benzene(e.g., Ethanox®330, from Ethyl Corp.). Exemplary secondary antioxidantsthat may replace or supplement a primary antioxidant includetris(2,4-di-tert-butylphenyl)phosphite (e.g., Irgafos® 168, Ciba-GeigyCorp.). Other antioxidants, including but not limited tomulti-functional antioxidants, are also useful herein and can serve asboth a primary and a secondary antioxidant. Irganox®1520 D, manufacturedby Ciba-Geigy is one example of a multifunctional antioxidant. Vitamin Eantioxidants, such as that sold by Ciba-Geigy under the tradenameIrganox®E17, are also useful in the present adhesives. Other suitableantioxidants include, without limitation, ascorbic acid, ascorbicpalmitate, tocopherol acetate, propyl gallate, butylhydroxyanisole,butylated hydroxytoluene,bis(1,2,2,6,6-pentamethyl-4-piperidinyl)-(3,5-di-tert-butyl-4-hydroxybenzyl)butylpropanedioate, (available as Tinuvin®144 from Ciba-Geigy Corp.)or a combination of octadecyl 3,5-di-tert-butyl-4-hydroxyhydrocinnamate(also known as octadecyl3-(3′,5′-di-tert-butyl-4′-hydroxyphenyl)propionate) (available asNaugard®76 from Uniroyal Chemical Co., Middlebury, Conn.) andbis(1,2,2,6,6-pentamethyl-4-piperidinylsebacate) (available asTinuvin®765 from Ciba-Geigy Corp.).

[0094] When included, the antioxidant can be present in amounts up to 2wt % of the adhesive composition, but will typically be present in therange of about 0.05 wt % to 1.5 wt.%.

pH Regulators

[0095] Compounds useful as pH regulators include, but are not limitedto, glycerol buffers, citrate buffers, borate buffers, phosphate buffersand citric acid-phosphate buffers. These regulators may be included soas to ensure that the pH of the skin-contacting adhesive composition iscompatible with that of an individual's body surface.

Pigments, Dyes and Refractive Particles

[0096] Pigments, dyes and refractive particles are typically included inan adhesive for aesthetic purposes, either to mimic the coloration ofthe skin surface or to provide an otherwise colorful adhesive.

[0097] There are numerous pigments and/or dyes that can be included inthe include adhesive. Preferably such additives will not leach out andstain or otherwise irritate the skin surface. Refractive particles areparticles that refract and reflect light striking the adhesive and thecolor of the reflected light changes as the angle at which the adhesiveis viewed is changed. Exemplary refractive particles are those made fromembossed, aluminized polyester.

Conductive Species

[0098] The skin-contacting adhesive may be rendered electricallyconductive for use in biomedical electrodes and other electrotherapycontexts, i.e., to attach an electrode or other electrically conductivemember to the body surface. For example, the adhesive may be used toattach a transcutaneous nerve stimulation electrode, an electrosurgicalreturn electrode, or an EKG electrode to a patient's skin or mucosaltissue. Such applications generally involve modifying the adhesivecomposition so as to contain a conductive species, which renders theadhesive composition conductive. Suitable conductive species includethose normally found in conductive adhesives used for application to theskin or other body surface, and include ionizable inorganic salts,organic compounds, or combinations of both. Examples of ionicallyconductive electrolytes include, by way of illustration and notlimitation, ammonium sulfate, ammonium acetate, monoethanolamineacetate, diethanolamine acetate, sodium lactate, sodium citrate,magnesium acetate, magnesium sulfate, sodium acetate, calcium chloride,magnesium chloride, calcium sulfate, lithium chloride, lithiumperchlorate, sodium citrate and potassium chloride, and redox couplessuch as a mixture of ferric and ferrous salts such as sulfates andgluconates, and combinations thereof. Although any amount of electrolytemay be present in the adhesive compositions of the invention, typicallythe electrolyte(s) will be present in an amount within the range ofabout 0.1-15 wt % of the adhesive.

[0099] Procedures for fabricating biomedical electrodes are well knownin the art and can be readily adapted for incorporating the adhesive ofthe invention into such electrodes. See for example, U.S. Pat. No.5,846,558 to Nielsen, et al., the disclosure of which is incorporatedherein by reference with respect to manufacturing details.

Antimicrobial Agents

[0100] Antimicrobial agents may be included to prevent spoilage uponstorage, i.e., to inhibit growth of microbes such as yeasts and molds.Suitable antimicrobial agents are typically selected from the groupconsisting of the methyl and propyl esters of p-hydroxybenzoic acid(i.e., methyl and propyl paraben), sodium benzoate, sorbic acid,imidurea, and combinations thereof.

Active Agents

[0101] One or more active agents can be included in the skin-contactingadhesive of the invention. Suitable active agents that may beincorporated into the adhesives of the invention, include the broadclasses of compounds normally delivered through body surfaces andmembranes such as, by way of illustration and not limitation: analepticagents; analgesic agents; antiarthritic agents; anticancer agents,including antineoplastic drugs; anticholinergics; anticonvulsants;antidepressants; antidiabetic agents; antidiarrheals; antihelminthics;antihistamines; antihyperlipidemic agents; antihypertensive agents;anti-infective agents such as antibiotics, antifungal agents, antiviralagents and bacteriostatic and bactericidal compounds; antiinflammatoryagents; antimigraine preparations; antinauseants; antiparkinsonismdrugs; antipruritics; antipsychotics; antipyretics; antispasmodics;antitubercular agents; antiulcer agents; anxiolytics; appetitesuppressants; attention deficit disorder and attention deficithyperactivity disorder drugs; cardiovascular preparations includingcalcium channel blockers, antianginal agents, central nervous systemagents, beta-blockers and antiarrhythmic agents; caustic agents; centralnervous system stimulants; cough and cold preparations, includingdecongestants; cytokines; diuretics; genetic materials; herbal remedies;hormonolytics; hypnotics; hypoglycemic agents; immunosuppressive agents;keratolytic agents; leukotriene inhibitors; mitotic inhibitors; musclerelaxants; narcotic antagonists; nicotine; nutritional agents, such asvitamins, essential amino acids and fatty acids; ophthalmic drugs suchas antiglaucoma agents; pain relieving agents such as anesthetic agents;parasympatholytics; peptide drugs; proteolytic enzymes;psychostimulants; respiratory drugs, including antiasthmatic agents;sedatives; steroids, including progestogens, estrogens, corticosteroids,androgens and anabolic agents; smoking cessation agents;sympathomimetics; tissue-healing enhancing agents; tranquilizers;vasodilators including general coronary, peripheral and cerebral;vessicants; and combinations thereof.

[0102] In a preferred embodiment, the active agent is selected from thegroup consisting of antibiotics, antifungal agents, antiinflammatoryagents, bacteriostatic and bactericidal compounds, caustic agents,keratolytic agents, pain relieving agents, proteolytic enzymes,tissue-healing enhancing agents, vasodilators, vessicants, andcombinations thereof. Typically the active agent(s) will be present in atherapeutically effective amount. Examples of drugs within these classesare set forth below.

[0103] The release of active agents “loaded” into the adhesiye of theinvention typically involves both absorption of water and desorption ofthe agent via a swelling-controlled diffusion mechanism. Activeagent-containing adhesives may be included in adhesive cushions, wounddressings, transdermal drug delivery devices and the like.

[0104] Antibiotics include antibiotics of the lincomycin family(referring to a class of antibiotic agents originally recovered fromstreptomyces lincolnensis); antibiotics of the tetracycline family(referring to a class of antibiotic agents originally recovered fromstreptomyces aureofaciens); sulfur-based antibiotics such as thesulfonamides; and so forth. Exemplary antibiotics of the lincomycinfamily include lincomycin itself(6,8-dideoxy-6-[[(1-methyl-4-propyl-2-pyrrolidinyl)-carbonyl]amino]-1-thio-L-threo-α-D-galacto-octopyranoside),clindamycin, the 7-deoxy, 7-chloro derivative of lincomycin (i.e.,7-chloro-6,7,8-trideoxy-6-[[(1-methyl-4-propyl-2-pyrrolidinyl)carbonyl]aamino]-1-thio-L-threo-α-D-galacto-octopyranoside), andpharmacologically acceptable salts and esters thereof. Exemplaryantibiotics of the tetracycline family include tetracycline itself4-(dimethylamino)-1,4,4α,5,5α,6,11,12α-octahydro-3,6,12,12α-pentahydroxy-6-methyl-1,11-dioxo-2-naphthacenecarboxamide),chlortetracycline, oxytetracycline, tetracycline, demeclocycline,rolitetracycline, methacycline and doxycycline and theirpharmaceutically acceptable salts and esters, particularly acid additionsalts such as the hydrochloride salt. Exemplary sulfur-based antibioticsinclude, but are not limited to, the sulfonamides sulfacetamide,sulfabenzamide, sulfadiazine, sulfadoxine, sulfamerazine,sulfamethazine, sulfamethizole, sulfamethoxazole, and pharmacologicallyacceptable salts and esters thereof, e.g., sulfacetamide sodium.

[0105] Exemplary antifungal agents include chloroxylenol, ciclopirox,clotrimazole, griseofulvine, ketoconazole, miconazole, tolnaftate,undecylenic acid, and so forth.

[0106] Exemplary antiinflammatory agents include corticosteroids andnonsteroidal anti-inflammatory drugs. Examples of nonsteroidalanti-inflammatory drugs include alminoprofen, benoxaprofen, butibufen,carprofen, fenbufen, fenoprofen, flurbiprofen, ibuprofen, indoprofen,ketoprofen, naproxen, oxaprozin, pirprofen, pranoprofen, suprofen,tiaprofenic acid, and so forth.

[0107] Exemplary bacteriostatic and bactericidal compounds include, arylmercury compounds such as phenylmercury borate or merbromin; alkylmercury compounds such as thiomersal;chloramine; chlorohexidine; halogencompounds such as iodine, iodopovidone complexes (e.g., complexes of PVPand iodine, also referred to as “povidine” and available under thetradename Betadine® from Purdue Frederick); iodide salts; organicnitrogen compounds such as 8-hydroxyquinoline, chlorquinaldol,clioquinol, ethacridine, hexetidine, ehlorhexedine and ambazone;organotin compounds such as tri-n-butyltin benzoate; oxidants such ashydrogen peroxide and potassium permanganate; phenols such as thymol,o-phenyl phenol, 2-benzyl-4-chlorophenol, hexachlorophen andhexylresorcinol; silver and silver-containing compounds such assulfadiazine, silver protein acetyltannate, silver nitrate, silveracetate, silver lactate, silver sulfate and silver chloride; sodiumhypochlorite; zinc and zinc salts; and so forth.

[0108] Exemplary caustic agents include podophyllin, and the like.

[0109] Exemplary keratolytic agents include lactic acid, salicylic acid,urea, and so forth.

[0110] Exemplary pain relieving agents include local or topicalanesthetics, including, but not limited to, acetamidoeugenol, alfadoloneacetate, alfaxalone, amucaine, amolanone, amylocaine, benoxinate,betoxycaine, biphenamine, bupivacaine, burethamine, butacaine, butaben,butanilicaine, buthalital, butoxycaine, carticaine, 2-chloroprocaine,cinchocaine, cocaethylene, cocaine, cyclomethycaine, dibucaine,dimethisoquin, dimethocaine, diperadon, dyclonine, ecgonidine, ecgonine,ethyl aminobenzoate, ethyl chloride, etidocaine, etoxadrol, β-eucaine,euprocin, fenalcomine, fomocaine, hexobarbital, hexylcaine,hydroxydione, hydroxyprocaine, hydroxytetracaine, isobutylp-aminobenzoate, kentamine, leucinocaine mesylate, levoxadrol,lidocaine, mepivacaine, meprylcaine, metabutoxycaine, methohexital,methyl chloride, midazolam, myrtecaine, naepaine, octacaine, orthocaine,oxethazaine, parethoxycaine, phenacaine, phencyclidine, phenol,piperocaine, piridocaine, polidocanol, pramoxine, prilocaine, procaine,propanidid, propanocaine, proparacaine, propipocaine, propofol,propoxycaine, pseudococaine, pyrrocaine, risocaine, salicyl alcohol,tetracaine, thialbarbital, thimylal, thiobutabarbital, thiopental,tolycaine, trimecaine, zolamine, and the like, with tetracaine,lidocaine and prilocaine being particularly suitable herein.

[0111] Exemplary proteolytic enzymes include those agents that areeffective wound cleansing agents, and include, for example, pepsin,trypsin, collagenase, chymotrypsin, elastase, carboxypeptidase,aminopeptidase, and the like.

[0112] Tissue-healing enhancing agents are also referred to in the artas tissue regenerative agents and include agents such as collagen;glycosaminoglycans such as hyaluronic acid, heparin, heparin sulfate andchondroitin sulfate; proteoglycans such as versican and biglycan;peptides such as fibronectin, vitronectin, osteopontin andthrombospondin, all of which contain the tripeptide sequence RGD(arginine-glycine-aspartic acid), a sequence generally associated withadhesive proteins and necessary for interaction with cell surfacereceptors; polypeptide growth factors such as platelet-derived growthfactor, fibroblast growth factor, transforming growth factor andinsulin-like growth factor; substrate adhesion molecules such asfibronectin, vitronectin and laminin; and so forth.

[0113] Exemplary vasodilators include those topical Vasodilators usefulfor increasing blood flow in the dermis, such as rubefacients andcounterirritants. Rubefacient agents include nicotinic acid, nicotinatessuch as methyl, ethyl, butoxyethyl, phenethyl and thurfyl nicotinate, aswell as the essential oils such as mustard, turpentine, cajuput andcapsicum oil, and components thereof.

[0114] Exemplary vessicants include cantharidin, and the like.

Permeation Enhancers

[0115] One or more permeation enhancers can be included in theskin-contacting adhesive of the invention. With some active agents, itmay be desirable to administer the agent along with a suitablepermeation enhancer in order to achieve a therapeutically effective fluxthrough the skin or mucosa. Selection of suitable permeation enhancerswill depend upon the agent being delivered, as well as the enhancer'scompatibility with the other components of the adhesive.

[0116] Exemplary permeation enhancers include, by way of illustrationand not limitation, sulfoxides such as dimethylsulfoxide anddecylmethylsulfoxide; ethers such as diethylene glycol monoethyl etherand diethylene glycol monomethyl ether; surfactants such as sodiumlaurate, sodium lauryl sulfate, cetyltrimethylammonium bromide,benzalkonium chloride, Poloxamer (231, 182, 184), Tween (20, 40, 60, 80)and lecithin; the 1-substituted azacycloheptan-2-ones, particularly1-n-dodecylcyclazacycloheptan- 2-one; alcohols such as ethanol,propanol, octanol, decanol, benzyl alcohol, and the like; fatty acidssuch as lauric acid, oleic acid and valeric acid; fatty acid esters suchas isopropyl myristate, isopropyl palmitate, methylpropionate, and ethyloleate; polyols and esters thereof such as propylene glycol, ethyleneglycol, glycerol, butanediol, polyethylene glycol, and polyethyleneglycol monolaurate; amides and other nitrogenous compounds such as urea,dimethylacetamide, dimethylformamide, 2-pyrrolidone,1-methyl-2-pyrrolidone, ethanolamine, diethanolamine andtriethanolamine; terpenes; alkanones; and organic acids, particularlysalicylic acid and salicylates, citric acid and succinic acid; andmixtures thereof.

[0117] H. Additional Elements

Backing Member

[0118] The skin-contacting adhesive of the invention may be formulatedso as to include a backing member, which can be laminated to theadhesive layer to serve as the outer surface of a dressing, cushion ortransdermal drug delivery device following application to the skin.Exemplary backing member materials include fibrous or porous sheetmaterials such as flannel, felt, cotton, polyesters, polyethylene,polypropylene, polyurethanes, polyether amides and the like. The backingmember is typically along the order of about 1-2.5 mils in thickness,but may be thinker or thinner as needed. If desired, the backing can bepigmented, metallized, or provided with a matte finish suitable forwriting.

[0119] In general, the material used for the backing layer should permitthe skin-contacting adhesive to follow the contours of the skin and beworn comfortably on areas of skin such as at joints or other points offlexure, that are normally subjected to mechanical strain with little orno likelihood of the adhesive disengaging from the skin due todifferences in the flexibility or resiliency of the skin and theadhesive.

[0120] Since the backing member covers a large surface area of theskin-contacting adhesive a highly water permeable backing can serve as asignificant conduit for water to enter the adhesive. The combination ofthe degree of water permeability into the backing and the ability of theadhesive to hold water for a required period of wearing time needs to bein balance. Thus if the adhesive is designed to hold enough water fromthe skin and from the periphery of the adhesive and not lose itscohesive-adhesive properties during the required period of wearing time,then a water impermeable backing is suitable for use.

[0121] However if it is preferred to have some water leave the adhesiveduring wearing then a water or moisture permeable backing is preferred.In that instance, the amount of water intrusion into the adhesive andthe moisture vapor transmission rate should be balanced. Also watershould not be too soluble in the backing layer otherwise the backinglayer may swell and either delaminate or cause the adhesive to lift-offprematurely. The outer surface of the backing ideally has a surfaceproperty that minimizes the ability of the adhesive to grab clothnormally used in socks, stockings or bed linen.

[0122] As noted above, when the adhesive is used in a dressing orcushion, the backing is preferably able to conform to the skin surfaceto which it is applied, for example, it can conform to the curvature ofthe ball and heel of a human foot when the foot is at rest. Duringwalking or running there will be intermittent increased compression,tension and shear forces on the backing and the adhesive. Use of aflexible and/or elastic backing member, minimizes the occurrence ofadhesive residue beyond the perimeter of the backing, which then wouldcause the dressing or cushion to stick to socks or bed coverings andpossibly become detached from the skin surface. Thus the coefficient offriction, compression and other elastic properties of the backing arealso important considerations.

[0123] In one embodiment of the invention, the backing is a polyurethanefilm having a thickness of about 1.5-2.0 mils. In another embodiment ofthe invention, the backing is a polymeric foam material. The porousnature of the foam can provide a depot of adhesive so that as pressureis applied to the skin-contacting adhesive, the adhesive formulation iscontinuously forced out of the pores to replenish the adhesive layerthat is in contact with the skin.

Release Liner

[0124] The skin-contacting adhesive of the invention may be formulatedso as to include a release liner, which can serve to protect theadhesive layer during storage and prior to use. The release linerpreferably peels away with an easy peel and does not stick aggressivelynor become difficult to remove from the adhesive during storage.Ideally, the release liner has adhesive properties that remain contactover time. The release liner can be made from numerous suitablematerials, but is preferably differentiated from the adhesive, cushion,etc., by material texture or design and is impermeable to the adhesivecomposition. Exemplary release liners include silicone or fluorocarbontreated materials, polyesters, polyvinyl chloride, cellulose acetate,polypropylene, polyethylene and polyethylene terephthalate films. Therelease liner is typically along the order of about 3 mils in thickness,but may be thinker or thinner as needed.

Applicator Tab or Mechanism

[0125] The skin-contacting adhesive of the invention may be formulatedso as to include an applicator tab or applicator mechanism, which isdesigned to facilitate application of the adhesive, cushion, etc., tothe appropriate skin location. For example, an applicator tab can be a 2mil polyolefin film.

[0126] III. CONFIGURATION AND SIZE

[0127] The skin contact area of the adhesive may be any size, but willtypically be within in the range of about 3-250 cm², and preferably inthe range of about 20-150 cm².

[0128] IV. FABRICATION

[0129] The skin-contacting adhesives of the invention are meltextrudable, and thus may be prepared using a simple blending andextruding process. The components of the adhesive are weighed out andthen admixed, for example using a Brabender, Haake or Baker PerkinsBlender, generally at a temperature within the range of about 90-160° C.Solvents may be added, but are not required. The resulting compositioncan be extruded using a single or twin-screw extruder. The compositioncan be extruded directly onto a substrate such as a backing member,covered with a release liner, and then pressed using, for example, aCarver press.

[0130] The thickness of the resulting skin-contacting adhesive, can havea variety of thicknesses, but typically will be in the range of about0.20-0.80 mm, more usually in the range of about 0.30-0.5 mm. In apreferred embodiment, the SCA, wound dressing or patch has a taperededge. FIG. 2 illustrates one type of tool that may be used to provide atapered edges. The tool has a solid portion 10, which is typicallymetal, and a cut-out section 20 that is configured to match the desireddimensions of the adhesive, wound dressing or cushion to be shaped.Cutting lines are shown as 30. The extruded precursor of the product(e.g., a thin layer of SCA surrounded by backing film from one side andrelease liner from another side) passes through a set of such punches,where the precursor is pressed, profiled and cut out to provide aplurality of tapered-edge products.

[0131] The order in which the various ingredients may be added into themixer is not critical to the invention, but in one preferred method theingredients are added in the following order: tackifying resin,hydrophobic polymer, elastomeric plasticizer, any optional materials,the clay particles and finally the cellulose derived polymers. Inanother preferred method, two mixtures are prepared in advance and thenmixed together with other components. Pellets of tackifier andhydrophobic polymers are premixed at ambient conditions (mixture “A”).Polysaccharide and clay are added to plasticizer and also premixed atroom temperature (mixture “B”). Components can then be loaded into themixer equipped with Benbary or sigma-blade rotors as follows: Time, Melttemperature, Speed, min ° C. rpm Stage 0 >130 20-100 Addition of mixtureA 1 >130 20-100 Stabilizer loaded 20 >130 20-100 Cellulose derivedpolymers added 40 130 20-100 Temperature decrease started 60 <130 20-100Addition of mixture B 80 <130 20-100 Additional agents introducing 110<130 0 End of mixing, discharge

[0132] The temperature may be increased or decreased with each additionto facilitate manufacture or to control the product characteristics. Forexample cellulose derived polymers are melted with formation ofanisotropic melt (130-140° C.). Triblock-copolymers as well asunsaturated polymers are softened in the same temperature range. Othercomponent can be added at lower temperature to prevent their possiblechemical decomposition. In this manner, the physical characteristics ofthe adhesive can be modified by altering the temperature regime,agitation speed and time.

[0133] The temperature profile can also be designed to provide for adesirable consistency of the SCA so that one is able to press the formededge and to cut the desired wound dressing or cushion products. Asuitable temperature for fabrication is around 70-110° C.

[0134] In one embodiment, the hydrophilic phase comprises at least onelow molecular weight cellulose derived polymer and is formulated by (1)blending the hydrophobic polymer, elastomeric plasticizer, tackifyingresin, and clay particles, to form a mixture; (2) heating the mixture toa temperature within the range of about 140-160° C.; and (3) adding thelow and high molecular weight cellulose derived polymers to form acomposition of the invention. One such process is exemplified asfollows. The tackifying resin is first heated to 90-95° C. with slowmixing (about 20-30 rpm), the temperature is then elevated to 95-105° C.and the hydrophobic polymer added, with slow mixing (about 20-30 rpm).The temperature is then raised to about 140-160° C. to obtain ahomogenous melt prior to addition of the elastomeric plasticizer, whichis then added with slow or rapid mixing (about 20-100 rpm). Whilemaintaining this temperature, any optional materials and the clayparticles can be added with rapid mixing. The mixture is then maintainedor cooled (if needed) to reach a temperature of about 135-150° C. andthe low and high molecular weight cellulose derived polymers are addedwith rapid mixing.

[0135] In another embodiment, the hydrophilic phase comprises at leastone naturally occurring polysaccharide and is formulated by (1)pre-mixing the tackifying resin and hydrophobic polymer to form a firstmixture; (2) pre-mixing the polysaccharide, clay particles, elastomericplasticizer to form a second mixture; (3) heating the first mixture to atemperature within the range of about 140-160° C.; (4) adding the highmolecular weight cellulose derived polymer to the first mixture; (5)cooling the first mixture; and (6) adding the second mixture to thefirst mixture to form a composition of the invention. One such processis exemplified as follows. The tackifying resin and hydrophobic polymerare pre-mixed at ambient temperature. The polysaccharide, clayparticles, elastomeric plasticizer are also premixed at ambienttemperature. The resin/polymer mixture is then heated to 140-160° C.with slow mixing. Optional ingredients may also be added at this point,for example an antioxidant, while maintaining the same temperature andspeed. The high molecular weight cellulose derived polymer is thenadded, while maintaining the same temperature and speed. The mixture isthen cooled to about 110-130° C. and the clay mixture is added. Optionalingredients, for example an adhesive agent, can also be added after theclay mixture.

[0136] Additional details of suitable mixing procedures are alsodescribed in the Examples.

[0137] V. SPECIFIC USES

[0138] The skin-contacting adhesive compositions of the invention findutility in numerous applications, such as in transdermal drug deliverydevices, topical and transdermal pharmaceutical formulations,pressure-relieving cushions (which may or may not be medicated),bandages, ostomy devices, prosthesis securing means, face masks, sound,vibration or impact absorbing materials, and the like. Also, thecompositions may be rendered electrically conductive by incorporation ofan electrically conductive material, and may thus be used for attachingan electroconductive particle, such as an electrode (e.g., atranscutaneous electric nerve stimulation electrode, an electrosurgicalreturn electrode or an EKG monitoring electrode), to an individual'sbody surface.

[0139] The skin-contacting adhesive compositions provide severalsignificant advantages, including:

[0140] (1) fabricated so as to be translucent, which enables one to viewthe extent of wound healing without removing the hydrogel from the bodysurface;

[0141] (2) displays of very high swelling upon contact with water;

[0142] (3) exhibits little or no cold flow during use; and

[0143] (4) readily modified during manufacture so that properties suchas adhesion, absorption, and translucence can be optimized.

[0144] A. Adhesive Cushion

[0145] The skin-contacting adhesive compositions of the invention areuseful in any number of applications wherein adhesion of a product to abody surface is called for or is desirable. One such embodiment is anadhesive cushion which comprises (a) a skin-contacting layer of anadhesive composition comprised of a hydrophobic phase and a hydrophilicphase and (b) a backing layer. The hydrophobic and hydrophilic phasesare as described above.

[0146] The backing layer is preferably non-occlusive (or “breathable”),i.e., is preferably permeable to moisture and will generally be made ofa flexible, resilient outer layer, fabricated from a translucent ortransparent, film, a foam pad or fibrous material such as fabric, with alayer of the adhesive composition of the invention laminated thereto forapplication to the skin surface. Exemplary backing players includetransparent polyurethane, transparent polyurethane coated with acrylicadhesive (to reinforce the connection between SCA and backing layer andfoamed polyurethane. Use of foamed or fabric backings may provide forincreased cushioning, however, use of such as backing will decrease thetransparency properties of the product. When moisture permeability isparticularly preferred, the backing layer should provide for anisotropicmoisture transportation, i.e., from the skin through the SCA and thebacking member, and then to the environment, but not vice versa, forexample during bathing.

[0147] Suitable cushions include, arch support pads, blister pads,bunion pads, callus pads, corn pads, elbow pads, finger pads, forearmpads, heel cushions, insoles, knee pads, metatarsal pads, shin pads, toepads, wrist pads, and so forth. Preferably, the adhesive cushion staysaffixed to the skin for at least seventy-two hours.

[0148] The adhesive cushion may further comprise a therapeuticallyeffective amount of an active agent, as defined above. In particular,active agents such as bacteriostatic and bactericidal compounds andantibiotic agents, and combinations thereof may be included in theadhesive composition.

[0149] The adhesive cushion can have a skin-contacting area in the rangeof about 3-250 cm², typically about 3-10 cm². A common shape foradhesive callus cushions is circular, and such patches will typicallyhave a diameter within the range of about 3.15-3.50 cm. Blister, bunionand corn cushions typically have an elliptic shape with tapered edges ofdifferent dimensions.

[0150] The adhesive cushion finds particular utility aspressure-relieving cushion for application to a foot. In one suchembodiment, the cushion contains an active agent for the treatment ofdicubitis, veinous and diabetic foot ulcers, or the like.

[0151] B. Wound Dressings

[0152] For wound dressings, suitable active agents are those useful forthe treatment of wounds, and include, but are not limited toantibiotics, antifungal agents, antiinflammatory agents, bacteriostaticand bactericidal compounds, pain relieving agents, proteolytic enzymes,tissue-healing enhancing agents, vasodilators, and combination thereof.Specific agents within these classes are set above.

[0153] In one embodiment, the wound dressing comprises a laminatedcomposite of a body facing layer having a body-contacting surface, andan outwardly facing non-occlusive backing layer, wherein at least aportion of the body-contacting surface is comprised of a skin-contactingadhesive comprised of a hydrophobic phase and a hydrophilic phase. Thehydrophobic and hydrophilic phases are as described above.

[0154] The wound dressing can be designed such that the entirebody-contacting surface is comprised of the adhesive, or the perimetercan be made up of the adhesive with an inner wound-contacting regionmade of a material such as a hydrogel.

[0155] The wound dressing may further include a backing layer and aremovable release liner that covers and is co-extensive with thebody-facing surface of the wound dressing.

[0156] It may be desirable to prepare the adhesive composition so thatit is substantially nontacky, or at most slightly tacky, when applied tothe body surface. In addition, the adhesive composition may furthercomprise a therapeutically effective amount of an active agent, asdefined above, that is suitable for application to a wound. Inparticular, active agents such as antibiotics, antifungal agents,antiinflammatory agents, bacteriostatic and bactericidal compounds, painrelieving agents, proteolytic enzymes, tissue-healing enhancing agents,vasodilators, and combination thereof may be included in the adhesivecomposition.

[0157] A typical skin-contacting area in the range of about 3-250 cm²,typically about 3-10 cm². Wound dressings are often rectangular inshape, and are commonly as large as 250 cm².

[0158] C. Transdermal Drug Delivery Devices

[0159] The skin-contacting adhesive composition also find utility whenincorporated into a transdermal drug delivery device. In one embodiment,such a device is comprised of a drug reservoir containing atherapeutically effective amount of an active agent, an outwardly facingbacking layer, and a means for affixing the device to a body surfacecomprising a skin-contacting adhesive composition comprised of ahydrophobic phase and a hydrophilic phase, as described above.

[0160] In the manufacture of such transdermal or transmucosal drugdelivery devices, the skin-contacting adhesive composition may be castor extruded onto a backing layer or release liner of such a device andwill serve as the skin contacting face of the “patch.” The drugreservoir may be separate from the adhesive composition or the adhesiveitself may be serve as a drug reservoir within the device.

[0161] Any number of active agents can be administered using these drugdelivery devices of the invention. The device will contain a quantity ofa pharmacologically active agent effective to provide the desired dosageover a predetermined delivery period and may also contain a carrier(e.g., a vehicle to solubilize the active agent), a permeation enhancer,if necessary, and optional excipients such as colorants, thickeningagents, stabilizers, surfactants and the like.

[0162] The transdermal drug delivery device may also contain a releaseliner or a rate-controlling membrane formed of a material selected tolimit the flux of one or more components contained in the drugformulation. Representative materials useful for formingrate-controlling membranes include polyolefins such as polyethylene andpolypropylene, polyamides, polyesters, ethylene-ethacrylate copolymer,ethylene-vinyl acetate copolymer, ethylene-vinyl methylacetatecopolymer, ethylene-vinyl ethylacetate copolymer, ethylene-vinylpropylacetate copolymer, polyisoprene, polyacrylonitrile,ethylene-propylene copolymer, polysiloxane-polycarbonate block copolymerand the like.

[0163] D. Other Products Requiring Adhesion To The Skin

[0164] The skin-contacting adhesive compositions of the invention arealso useful in a host of other contexts, e.g., as adhesives for affixingmedical devices, diagnostic systems and other devices to be affixed to abody surface, and in any other application wherein adhesion to a bodysurface is necessary or desired. The adhesive compositions are alsouseful as sealants for ostomy devices, prostheses, and face masks, assound, vibration or impact absorbing materials, as carriers in cosmeticand cosmeceutical gel products, and will have other uses known to orascertainable by those of ordinary skill in the art, or as yetundiscovered.

[0165] The practice of the present invention will employ, unlessotherwise indicated, conventional techniques of polymer chemistry,adhesive manufacture, and hydrogel preparation, which are within theskill of the art. Such techniques are fully explained in the literature.

EXAMPLES

[0166] The following examples are put forth so as to provide those ofordinary skill in the art with a complete disclosure and description ofhow to make and use the compounds of the invention, and are not intendedto limit the scope of what the inventors regard as their invention.Efforts have been made to ensure accuracy with respect to numbers (e.g.,amounts, temperature, etc.) but some errors and deviations should beaccounted for. Unless indicated otherwise, parts are parts by weight,temperature is in ° C. and pressure is at or near atmospheric.

Abbreviations and Trademarks

[0167] The following abbreviations and tradenames are used in theexamples: Adhesive Agent Low molecular weight polyisobutylene rubberAPFR Alkylphenolformaldehide resin SP 1055 BR 065 High molecular weightbutyl rubber (Exxon) DCP Dicumyl peroxide Cloisite Na⁺ Natural clay(Southern Clay Products) Cloisite 15A Natural clay modified withdioctadecylammonium (Southern Clay Products) Escorez 5380 Hydrocarbonresin (Exxon) GF HPC polymer (available under the tradename Klucel ®,Hercules Inc.); molecular weight of about 370,000 g/mole HF HPC polymer(Klucel ®); molecular weight of about 1,150,000 g/mole HPCHydroxypropylcellulose HPMC Hydroxypropylmethylcellulose Irganox ® 1010Antioxidant, Tetrakis [methylene (3,5-di-tert-butyl-4-hydroxyhydrocinnamate)] methane (Ciba-Geigy) Isolene ® 400 Cis-1,4polyisoprene (Elementis Specialties Performance Polymers) Kalene 1300Low molecular weight butyl rubber (Elementis Specialties PerformancePolymers) LF HPC polymer (Klucel ®); molecular weight of about80,000-95,000 g/mole JF HPC polymer (Klucel ®); molecular weight ofabout 140,000 g/mole MF HPC polymer (Klucel ®); molecular weight ofabout 850,000 g/mole Na—CMC Sodium carboxymethylcellulose Natsyn ® 2210Polyisoprene rubber (Goodyear Tire and Rubber) Paraffin oil Oil extenderPIB Polyisobutylene PFR Phenolformaldehyde resin Regalite ® 9100Partially hydrogenated hydrocarbon resin (Hercules) Styrene plasticizerStyrene-isoprene copolymer (Kraton) Vector 4111 Styrene-isoprene-styreneblock copolymer (available from Dexco Polymers); styrene:isoprene ratioof 18:82) Vector 4114 Styrene-isoprene-styrene block copolymer (DexcoPolymers); 42 wt % styrene-isoprene diblock; overall styrene:isopreneratio of 15:85 Wingtack 86 Synthetic polyterpene resin (Goodyear Tireand Rubber)

EXAMPLE 1

[0168] The following are exemplary formulations of skin-contactingadhesive of the invention. The prepared formulations were alltranslucent, as determined visually.

[0169] The manufacture of Formulations 1 and 2 involved adding thecellulose derived polymers at a high temperature (>130° C.). In thismanner, the polymers are melted, forming liquid crystalline droplets,which are stretched at mixing giving fibers (high MW cellulose derivedpolymer) or ellipsoids (low MW cellulose derived polymer). Ingredient Wt% Formulation 1 Hydrophobic polymer: Vector 4111 44.69 Elastomericplasticizer: Styrene plasticizer 28.86 Tackifying resin: Regalite ® 91001.86 High MW Cellulose derived polymer: MF 9.31 Low MW Cellulose derivedpolymer: LF 9.31 Clay particles: Cloisite Na⁺ 5.6 Other ingredients:Irganox ® 1010 0.37 Formulation 2 Hydrophobic polymer: Vector 4111 45.11Elastomeric plasticizer: Styrene plasticizer 30.07 Tackifying resin:Regalite ® 9100 1.88 High MW Cellulose derived polymer: MF 9.40 Low MWCellulose derived polymer: HPMC 9.40 Clay particles: Cloisite 15A 3.76Other ingredients: Irganox ® 1010 0.37

Water Uptake Studies

[0170] A water uptake study was conducted on skin-contacting adhesivesprepared in Example 1 and the swell ratio and water uptake werecalculated.

[0171] Procedure: Each skin-contacting adhesive was die-cut into circles25 mm in diameter. The cross-sectional area of the adhesive was measuredusing a ruler while the thickness of the patch was determined using aMitotoyo Digimatic Micrometer at three points across the sample. Theweight of the dry adhesive samples was also determined using a 5-decimalpoint microbalance. Each sample was then immersed in 20 ml ofphosphate-buffered saline (0.9% w/v, 0.1M phosphate buffer pH 7.40) at37° C. The weight and dimensions of each swollen adhesive sample weredetermined after 24 hours water uptake, after dabbing off excesssolution. The weight difference represents the amount of water imbibedby the material. The samples were dried at 90° C. for 2 to 4 hoursbefore taking their weight and dimensions to obtain the degree ofdissolution of the patch. Each experiment was repeated three times, andthe indicated values are averages. Results are set forth below.Formulation % Water Uptake Swell Ratio Formulation 1 96.15 1.46Formulation 2 48.6 1.21

Tack Studies

[0172] Tack studies were conducted and the probe tack measurements wereprovided from a stainless steel probe having a diameter of approximately0.5 cm using the following conditions: applied contact weight of 177 g,dwell time of 10 seconds, withdrawal speed of 5.0 cm/sec.

[0173] Results are set forth below. Tack (g) Formulation 0.2 cm/sec 0.01cm/sec Formulation 1 340 120 Formulation 2 284.3 102.3

EXAMPLE 2

[0174] The following is another exemplary formulation of theskin-contacting adhesive of the invention. The prepared formulation wastranslucent, as determined visually.

[0175] The manufacture of Formulation 3 involved adding the cellulosederived polymers at a lower temperature (about 100° C). In this manner,the polymers behaved like a powder. Formulation 3 Ingredient Wt %Hydrophobic polymer: Vector 4111 45.54 Elastomeric plasticizer: Styreneplasticizer 29.41 Tackifying resin: Regalite ® 9100 1.9 High MWCellulose derived polymer: MF 9.49 Low MW Cellulose derived polymer: LF9.49 Clay particles: Cloisite Na⁺ 3.8 Other ingredients: Irganox ® 10100.38

Water Uptake Studies

[0176] A water uptake study of Formulation 3 was conducted as describedin Example 1. The percentage water uptake was 35.6, with a swell ratioof 1.22

Tack Studies

[0177] A tack study was conducted as described in Example 1. Formulation3 had a tack of 375.7 g at 0.2 cm/sec and 142.3 g at 0.01 cm/sec.

EXAMPLE 3

[0178] The following is an additional exemplary formulation of theskin-contacting adhesive of the invention. The prepared formulation wastranslucent, as determined visually.

[0179] The manufacture of Formulation 4 involved adding the cellulosederived polymers at a high temperature (above 130° C.) so the polymersbehaved like liquid crystals. Formulation 4 Ingredient Wt % (temp/rpm)Tackifying resin: Regalite ® 9100 27.97 (94/23) Hydrophobic polymer:Vector 4111 9.57 (100/23) Hydrophobic polymer: Vector 4114 9.54 (101/23)Elastomeric plasticizer: Styrene plasticizer 14.5 (151/31) Other:Adhesive Agent 1.5 (150/58) Clay particles: Cloisite Na⁺ 3.0 (144/100)Low MW Cellulose derived polymer: JF 11.97 (140/100) High MW Cellulosederived polymer: GF 17.95 (144/100) High MW Cellulose derived polymer:HF 4.0 (146/100)

[0180] The ingredients are listed in the order in which they were addedto the mixture. “Temp” refers to the temperature (° C.) of the mixtureor melt when the particular ingredient was added, while “rpm” refers tothe revolutions per minute of the mixture when the particular ingredientwas added. Such temperatures and rpm values were maintained until thenext ingredient was added.

[0181] After the final addition of clay particles, mixing was continuedfor 15 minutes at the final temperature of 144° C., and for 3 minutes at150° C.

Tack Studies

[0182] Tack studies were conducted on Formulation 4 as described inExample 1. The speed was 0.2 cm/sec with a 10 second dwell time. Resultsare set forth below. Sample # Sample thickness (mil) Tack (g) 1 23.0 6052 24.5 616 3 25.0 797 Average 24.16 672.66 % RSD 4.31 16.0

EXAMPLE 4

[0183] The following is an additional exemplary formulation of theskin-contacting adhesive of the invention. The prepared formulation wastranslucent, as determined visually.

[0184] The manufacture of Formulation 5 involved adding the cellulosederived polymers at a high temperature (above 130° C.) so the polymersbehaved like liquid crystals. Formulation 5 Ingredient Wt (g) Temp rpmWt % Tackifying resin: Regalite ® 9100 15.5  94  20 28.1 Hydrophobicpolymer: Vector 4111 5.25 100  20 9.51 Hydrophobic polymer: Vector 41145.25 101  20 9.51 Elastomeric plasticizer: Styrene plasticizer 4.0 148 20 7.25 Elastomeric plasticizer: Isolene ® 400 4.0 146  20 7.25 Other:Adhesive Agent 0.833 138-  20- 1.51 140 100 Clay particles: Cloisite Na⁺1.65 144 100 2.99 Low MW Cellulose derived polymer: JF 6.6 138- 10011.96 140 High MW Cellulose derived polymer: GF 9.9 144 100 17.94 HighMW Cellulose derived polymer: HF 2.2 146 100 3.98

[0185] The ingredients are listed in the order in which they were addedto the mixture. “Temp” refers to the temperature (° C.) of the mixtureor melt when the particular ingredient was added, while “rpm” refers tothe revolutions per second of the mixture when the particular ingredientwas added. Such temperatures and rpm values were maintained until thenext ingredient was added. After the final addition of clay particles,mixing was continued for 15 minutes at the final temperature of 146° C.

Tack Studies

[0186] Tack studies were conducted as described in Example 1. The speedwas 0.2 cm/sec with a 10 second dwell time. Results are set forth below.Sample # Sample thickness (mil) Tack (g) 1 17.5 656 2 20.5 614 3 19.5519 Average 19.16 596.3 % RSD 7.97 11.7

EXAMPLE 5

[0187] The following Formulations 6-8 are additional exemplaryformulations of the skin-contacting adhesive of the invention.Formulation 6 7 8 Ingredient Wt % Wt % Wt % Hydrophobic polymer: Vector4111 20.0 19.1 18.0 Tackifying resin: Regalite ® 9100 29.5 28.1 —Tackifying resin: Escorez 5380 — — 35.0 Elastomeric plasticizer: Styreneplasticizer 15.0 14.3 10.0 Other: Adhesive Agent 1.5 1.5 — Clayparticles: Cloisite Na⁺ 4.0 3.0 3.0 Low MW Cellulose derived polymer: JF12.0 12.0 12.0 High MW Cellulose derived polymer: GF 18.0 18.0 18.0 HighMW Cellulose derived polymer: HF — 4.0 4.0

[0188] The adhesive strength of these formulations was measured anddetermined to be 650 ±20 N/m, 800±20 N/m, and 450÷500 N/m forFormulations 8, 9 and 10, respectively.

EXAMPLE 6

[0189] The following Formulations 9-13 are additional exemplaryformulations of the skin-contacting adhesive of the invention.Formulation 9 10 11 12 13 Ingredient Wt % Wt % Wt % Wt % Wt %Hydrophobic polymer: Vector 4114 20.0 20.0 — 20.0 18.0 Hydrophobicpolymer: Vector 4111 — — 21.0 — — Tackifying resin: Regalite ® 9100 25.525.5 — 25.5 25.5 Tackifying resin: Escorez 5380 — — 30.0 — — Elastomericplasticizer:  5.0 10.0 10.0 15.0 15.0 Isolene ® 400 Elastomericplasticizer: —  5.0 — — — Styrene plasticizer Other: Adhesive Agent  1.5 1.5 —  1.5  1.5 Clay particles: Cloisite Na⁺  8.0  8.0  4.0 10.0 20.0High MW Cellulose derived — — —  5.0 10.0 polymer: GF Naturallyoccurring 15.0 15.0 — 20.0  5.0 polysaccharide: Agar Naturally occurring— — 20.0 — — polysaccharide: Starch Other: Paraffin oil — —  5.0 — —High MW Cellulose derived 15.0 12.0 10.0 — — polymer: MF Low MWCellulose derived 10.0  3.0 —  3.0  5.0 polymer: LF Other: Irganox ®1010 ˜0.1 ˜0.1 ˜0.1 ˜0.1 ˜0.1

[0190] The ingredients in the table below are listed in the order inwhich they were added to the mixture. Pellets of Regalite®9100 andVector 4114 were premixed at ambient temperature to form “Mixture A”.Agar and the clay particles were added to polyisoprene and styreneplasticizers, and premixed at ambient temperature to form “Mixture B”.Ingredient Temp rpm Mixture A 150 30 GF, MF or LF 150 30 Mixture B 12030 Adhesive Agent 120 30

[0191] “Temp” refers to the temperature (° C.) of the mixture or meltwhen the particular ingredient was added, while “rpm” refers to therevolutions per minute of the mixture when the particular ingredient wasadded. Such temperatures and rpm values were maintained until the nextingredient was added, except that the temperature was raised to 120° C.after the addition of GF. After the final addition of clay particles,mixing was continued for 30 minutes at the final temperature of 120° C.

[0192] Formulations 9-13 were tested for water uptake, moisturepenetration rate, adhesion (peel and tack testers), as well as theirwearing properties as callus, corn, and bunion cushions. The wearingresults of various groups of people for callus cushion are presentedbelow. Number of Avg. number Avg. wearing Formulation Volunteers* ofshowers time, hours  9 3-MY 2.7 69.3 4-MO 3.5 85.2 3-FY 2.9 70.3 2-FO3.2 74.5 10 2-MY 3.0 70.5 3-MO 3.3 75.3 3-FY 2.3 52.3 3-FO 3.3 73.3 113-MY 2.3 62.0 4-MO 2.0 48.0 2-FY 1.5 44.5 4-FO 1.8 48.2 12 3-MY 3.0 72.03-MO 3.0 74.0 3-FY 2.7 68.3 4-FO 3.2 78.2 13 2-MY 2.5 58.5 4-MO 2.7 66.23-FY 2.3 52.3 2-FO 2.7 63.5

EXAMPLE 7

[0193] This example describes using unsaturated elastomers accompaniedby plasticizers, tackifiers, oil extender and curing agents ashydrophobic phase, and various cellulose derivatives in the hydrophilicphase. The following Formulations 14-18 are additional exemplaryformulations of the skin-contacting adhesive of the invention.Formulation 14 15 16 17 18 Ingredient Wt % Wt % Wt % Wt % Wt %Hydrophobic polymer: BR 065 — 30.0 30.0 22.0 — Elastomeric plasticizer:Kalene 1300 — 20.0 27.0 — — Elastomeric plasticizer: PIB — — — 25.0 —Hydrophobic polymer: 20.0 — — — 25.6 Natsyn ® 2210 Elastomericplasticizer: 15.0 — — — 17.1 Isolene ® 400 Tackifying resin: Regalite —12.0 10.0 13.5 21.3 Tackifying resin: Wingstack 86 15.0 — — — — High MWCellulose derived 20.0 — 22.0 — — polymer: Na-CMC Other: PFR CuringAgent —  4.0 —  4.5 — Other: APFR Curing Agent —  3.0  3.0 — — Other:DCP Curing Agent  5.0 — — —  2.0 Other: Paraffin oil  5.0 — — — — Low MWCellulose derived — 13.0  5.0 — 12.0 polymer: LF Low MW Cellulosederived 16.0 — — 17.0 — polymer: JF High MW Cellulose derived — — — —14.0 polymer: GF High MW Cellulose derived — 10.0 — — — polymer: MF HighMW Cellulose derived —  3.0 — 15.0  4.0 polymer: HF Clay particles:Cloisite 15A  4.0  5.0  3.0  3.0  4.0

[0194] In order to effectively apply these formulations to locations onthe body that are subjected to constant or varying pressure, it ispreferable to select a curing regime (content of crosslinker, time,temperature) that will diminish cold flow. The measurement of the changein viscosity over time provides a useful and informative estimation ofcuring kinetics. As an example, rheokinetic curves for the precursor offormulation 17 (BR/PIB/Regalite+4.5% APFR) at 150° C. (Curve 1) and forthe complete formulation 17 at 150° C. (Curve 2), 160° C. (Curve 3) and170° C. (Curve 4), as shown in FIG. 3. Curve 1 shows that there is aninduction period, a region of sharp viscosity increase, and a plateauregion. It is believed that the plateau region corresponds to themaximum attainable at the given conditions of the density of thechemical network. Introducing the hydrophilic cellulose derived polymersleads to the disappearance of the induction period (Curve 2). Anincrease of curing temperature to 160° C. (Curve 3) and 170° C. (Curve4) results in reducing the time to reach the plateau region from 80 to40 min.

[0195] The squeeze-recoil method provides useful information as to theabsence of any cold flow. According to this method, a flat sample issqueezed under constant force for a set time, the force is removed andthe elastic recovery of the sample measured. Two sets of squeeze-recoilcurves are shown in FIG. 4. Curve 1 describes the elastic properties offormulation 17, cured for 40 minutes at 150° C. Curve 2 describes theelastic properties of formulation 17, cured for 40 minutes at 170° C.The elastic recovery reaches ˜40% at 150° C. and >90% at 170° C. Usingthis method, it is therefore possible to estimate the optimal curingconditions.

[0196] In another embodiment of the invention, the hydrophobic phase canbe cured by means of UV irradiation. The curing kinetics can the bereadily measured by standard swelling techniques, and the completenessof the curing process can be measured by the squeeze-recoil method.

[0197] Formulations 14-18 were characterized by water uptake, initialtack, adhesion, and wearing properties. All exhibited properties thatwould render them suitable for use as wound dressings and cushionproducts. In addition, the formulations containing a polyisopreneelastomeric plasticizer (Natsyn® 2210 or Isolene® 400) maintained theirtransparency even after water uptake test.

[0198] All patents, patent applications, journal articles and otherreferences cited herein are incorporated by reference in theirentireties.

[0199] It is to be understood that while the invention has beendescribed in conjunction with the preferred specific embodiments hereof,the foregoing description, as well as the examples which are intended toillustrate and not limit the scope of the invention, it should beunderstood by those skilled in the art that various changes may be madeand equivalents may be substituted without departing from the scope ofthe invention. Other aspects, advantages and modifications will beapparent to those skilled in the art to which the invention pertains.

[0200] Accordingly, the scope of the invention should therefore bedetermined with reference to the appended claims, along with the fullrange of equivalents to which those claims are entitled.

We claim:
 1. A skin-contacting adhesive composition comprised of ahydrophobic phase and a hydrophilic phase, wherein: (a) the hydrophobicphase comprises a hydrophobic polymer, at least one elastomericplasticizer and a tackifying resin; and (b) the hydrophilic phasecomprises: i) at least one material selected from the group consistingof low molecular weight cellulose derived polymers and naturallyoccurring polysaccharides; ii) at least one high molecular weightcellulose derived polymer; and iii) reinforcing clay particles.
 2. Thecomposition of claim 1 which comprises about 50-80 wt % hydrophobicphase and about 20-50 wt % hydrophilic phase.
 3. The composition ofclaim 2 which comprises about 60-70 wt % hydrophobic phase and about30-40 wt % hydrophilic phase.
 4. The composition of claim 1 whichcomprises about 10-50 wt % hydrophobic polymer; about 5-40 wt %elastomeric plasticizer; about 0.5-40 wt % tackifying resin; about 5-40wt % high molecular weight cellulose derived polymers; about 2-30 wt %reinforcing clay particles; and about 0-20 wt % optional ingredients. 5.The composition of claim 4 which comprises about 15-46 wt % hydrophobicpolymer; about 5-31 wt % elastomeric plasticizer; about 1-35 wt %tackifying resin; and about 5-32 wt % high molecular weight cellulosederived polymers; about 3-20 wt % reinforcing clay particles; and about0.1-10 wt % optional ingredients.
 6. The composition of claim 4 whichcomprises about 2-40 wt % naturally occurring polysaccharides.
 7. Thecomposition of claim 6 which comprises about 5-20 wt % naturallyoccurring polysaccharides.
 8. The composition of claim 4 which comprisesabout 1-20 wt % low molecular weight cellulose derived polymers.
 9. Thecomposition of claim 8 which comprises about 3-17 wt % low molecularweight cellulose derived polymers.
 10. The composition of claim 1wherein the weight ratio of the hydrophobic phase and the hydrophilicphase is selected so as to optimize the adhesive strength, cohesivestrength and water sorption of the composition.
 11. The composition ofclaim 1 wherein the weight ratio of the high molecular weight cellulosederived polymers, low molecular weight cellulose derived polymers ornaturally occurring polysaccharides, and the reinforcing clay particlesis selected so as to optimize the adhesive strength, cohesive strengthand water sorption of the composition.
 12. The composition of claim 1wherein the weight ratio of the hydrophobic polymer, elastomericplasticizer and tackifying resin is selected so as to optimize theadhesive strength, cohesive strength and water sorption of thecomposition.
 13. The composition of claim 1 wherein the weight ratio ofthe hydrophobic phase and the hydrophilic phase is selected so as torender the composition translucent.
 14. The composition of claim 1wherein the weight ratio of the high molecular weight cellulose derivedpolymers, low molecular weight cellulose derived polymers, naturallyoccurring polysaccharides, and the reinforcing clay particles isselected so as to render the composition translucent.
 15. Thecomposition of claim 1 wherein the weight ratio of the hydrophobicpolymer, elastomeric plasticizer and tackifying resin is selected so asto render the composition translucent.
 16. The composition of claim 1wherein the hydrophobic polymer is selected from the group consisting ofbutadiene acrylonitrile rubber, butyl rubbers, ethylene-propylene-dieneterpolymers, isobutylene-isoprene copolymers, natural rubber adhesives,polychloroprenes, polyisobutylenes, polyisoprenes, polysiloxanes,styrene-butadiene-styrene block copolymers, styrene-isoprene-styreneblock copolymers, vinyl ether polymers, and combinations thereof. 17.The composition of claim 16 wherein the hydrophobic polymer selectedfrom the group consisting of butyl rubbers, polyisoprenes,styrene-butadiene-styrene block copolymers, styrene-isoprene-styreneblock copolymers, and combinations thereof.
 18. The composition of claim1 wherein the hydrophobic polymer is selected from the group consistingof styrene-butadiene-styrene block copolymers andstyrene-isoprene-styrene block copolymers, and further comprises astyrene-isoprene block copolymer.
 19. The method of claim 18 wherein thehydrophobic polymer mixture comprises up to 45 wt % of thestyrene-isoprene block copolymer.
 20. The composition of claim 1 whereinthe elastomeric plasticizer is selected from the group consisting of lowmolecular weight polyisobutylenes, low molecular weight polyisoprenerubbers, styrene-based plasticizers, and combinations thereof.
 21. Thecomposition of claim 20 wherein the styrene-based plasticizer isselected from the group consisting of styrene-isoprene block copolymers,styrene-butadiene block copolymers, and combinations thereof.
 22. Thecomposition of claim 21 wherein the elastomeric plasticizer furthercomprises a low molecular weight polyisoprene rubber.
 23. Thecomposition of claim 1 wherein the tackifying resin is a non-polartackifying resin selected from the group consisting of hydrogenatedhydrocarbon resins, hydrocarbon resins and synthetic polyterpene resins.24. The composition of claim 1 wherein the cellulose derived polymersare selected from the group consisting of hydroxypropylcellulose,hydroxypropylmethylcellulose and sodium carboxymethylcellulose.
 25. Thecomposition of claim 1 wherein the high molecular weight cellulosederived polymer has a molecular weight within the range of about300-1,150 kg/mole.
 26. The composition of claim 1 wherein the lowmolecular weight cellulose derived polymer has a molecular weight withinthe range of about 80-140 kg/mole.
 27. The composition of claim 1wherein the hydrophilic phase comprises at least one low molecularweight cellulose derived polymer and the weight ratio of low molecularweight cellulose derived polymers to high molecular weight cellulosederived polymers is about 1:1 to 1:2.
 28. The composition of claim 1wherein the hydrophilic phase comprises at least one naturally occurringpolysaccharide and the weight ratio of naturally occurringpolysaccharides to cellulose derived polymers is about 1:1 to 2:1. 29.The composition of claim 28 wherein the naturally occurringpolysaccharide is selected from the group consisting of agars,alginates, carrageenans, chitin, chitosan, glucomannan, gum guar, gellangum, locust bean gum, pectins, pullulan, starches and xanthans, andcombinations thereof.
 30. The composition of claim 29 wherein thenaturally occurring polysaccharide is agar or starch.
 31. Thecomposition of claim 1 wherein the hydrophilic phase comprises a mixtureof a low molecular weight cellulose derived polymer and a naturallyoccurring polysaccharide.
 32. The composition of claim 1 wherein thereinforcing clay particles have an average diameter of about <15 μ. 33.The composition of claim 1 wherein the clay particles are comprised of aphyllosilicate.
 34. The composition of claim 33 wherein thephyllosilicate is montmorillonite.
 35. The composition of claim 1 whichfurther comprises an active agent.
 36. The composition of claim 35wherein the active agent is selected from the group consisting ofantibiotics, antifungal agents, antiinflammatory agents, bacteriostaticand bactericidal compounds, caustic agents, keratolytic agents, painrelieving agents, proteolytic enzymes, tissue-healing enhancing agents,vasodilators, vessicants, and combinations thereof, and is present in atherapeutically effective amount.
 37. The composition of claim 36 whichfurther comprises a permeation enhancer.
 38. The composition of claim 1which further comprises at least one additive selected from the groupconsisting of adhesive agents, antioxidants, absorbent fillers, curingagents, preservatives, pH regulators, pigments, dyes, refractiveparticles, conductive species and antimicrobial agents.
 39. Thecomposition of claim 1 which is prepared by a blending and extrudingprocess.
 40. The composition of claim 39 wherein the hydrophilic phasecomprises at least one low molecular weight cellulose derived polymer,and wherein: (1) the hydrophobic polymer, elastomeric plasticizer,tackifying resin, and clay particles are blended to form a mixture; (2)the mixture is heated to a temperature within the range of about140-160° C.; and (3) the low and high molecular weight cellulose derivedpolymers are added to the mixture to form the composition.
 41. Thecomposition of claim 39 wherein the hydrophilic phase comprises at leastone naturally occurring polysaccharide, and wherein (1) the tackifyingresin and hydrophobic polymer are mixed to form a first mixture; (2) thepolysaccharide, clay particles, and elastomeric plasticizer are mixed toform a second mixture; (3) the first mixture is heated to a temperaturewithin the range of about 140-160° C.; (4) the high molecular weightcellulose derived polymer added to the first mixture; (5) the firstmixture is cooled; and (6) adding the second mixture to the firstmixture to form the composition.
 42. A skin-contacting adhesivecomposition comprised of a hydrophobic phase and a hydrophilic phase,wherein: (a) the hydrophobic phase comprises: a hydrophobic polymerselected from the group consisting of butadiene acrylonitrile rubber,butyl rubbers, ethylene-propylene-diene terpolymers,isobutylene-isoprene copolymers, natural rubber adhesives,polychloroprenes, polyisobutylenes, polyisoprenes, polysiloxanes,styrene-butadiene-styrene block copolymers, styrene-isoprene-styreneblock copolymers, vinyl ether polymers, and combinations thereof; atleast one elastomeric plasticizer and a tackifying resin; and (b) thehydrophilic phase comprises: i) at least one material selected from thegroup consisting of low molecular weight cellulose derived polymers andnaturally occurring polysaccharides; ii) at least one high molecularweight cellulose derived polymer; and iii) reinforcing clay particles.43. The composition of claim 42 which comprises about 50-80 wt %hydrophobic phase and about 20-50 wt % hydrophilic phase.
 44. Thecomposition of claim 42 wherein the hydrophobic polymer is selected fromthe group consisting of butyl rubbers, polyisoprenes,styrene-butadiene-styrene block copolymers, styrene-isoprene-styreneblock copolymers, and combinations thereof.
 45. The composition of claim42 wherein the hydrophobic polymer is selected from the group consistingof styrene-isoprene-styrene block copolymers andstyrene-butadiene-styrene block copolymers, and further comprises astyrene-isoprene block copolymer.
 46. The composition of claim 42wherein the elastomeric plasticizer is selected from the groupconsisting of low molecular weight polyisobutylenes, low molecularweight polyisoprene rubbers, styrene-based plasticizers, andcombinations thereof.
 47. The composition of claim 42 wherein thetackifying resin is selected from the group consisting of hydrogenatedhydrocarbon resins, hydrocarbon resins and synthetic polyterpene resins.48. The composition of claim 42 wherein the high molecular weightcellulose derived polymer is selected from the group consisting ofhydroxypropylcellulose, hydroxypropylmethylcellulose and sodiumcarboxymethylcellulose.
 49. The composition of claim 42 wherein thehydrophilic phase comprises at least one low molecular weight cellulosederived polymer selected from the group consisting ofhydroxypropylcellulose, hydroxypropylmethylcellulose and sodiumcarboxymethylcellulose.
 50. The composition of claim 42 wherein thehydrophilic phase comprises at least one naturally occurringpolysaccharide selected from the group consisting of agars, alginates,carrageenans, chitin, chitosan, glucomannan, gum guar, gellan gum,locust bean gum, pectins, pullulan, starches and xanthans, andcombinations thereof.
 51. The composition of claim 42 wherein the clayparticles are comprised of montmorillonite.
 52. The composition of claim42 which further comprises a low molecular weight polyisobutylene. 53.The composition of claim 42 which further comprises an active agentselected from the group consisting of antibiotics, antifungal agents,antiinflammatory agents, bacteriostatic and bactericidal compounds,caustic agents, keratolytic agents, pain relieving agents, proteolyticenzymes, tissue-healing enhancing agents, vasodilators, vessicants, andcombinations thereof, and is present in a therapeutically effectiveamount.
 54. An adhesive cushion for application to the skin, comprising:(a) a skin-contacting layer of an adhesive composition comprised of ahydrophobic phase and a hydrophilic phase, wherein: (i) the hydrophobicphase comprises a hydrophobic polymer, at least one elastomericplasticizer and a tackifying resin; and (ii) the hydrophilic phasecomprises: 1) at least one material selected from the group consistingof low molecular weight cellulose derived polymers and naturallyoccurring polysaccharides; 2) at least one high molecular weightcellulose derived polymer; and 3) reinforcing clay particles; andlaminated thereto, (b) a backing layer.
 55. The adhesive cushion ofclaim 54 which further comprises a therapeutically effective amount ofan active agent.
 56. The adhesive cushion of claim 55 wherein the activeagent is selected from the group consisting of bacteriostatic andbactericidal compounds, antibiotic agents, and combinations thereof. 57.The adhesive cushion of claim 54 which is an arch support pad, blisterpad, bunion pad, callus pad, corn pad, elbow pad, finger pad, forearmpad, heel cushion, insole, knee pad, metatarsal pad, shin pad, toe pador wrist pad.
 58. The adhesive cushion of claim 54 wherein the backinglayer is non-occlusive and is comprised of a flexible material.
 59. Theadhesive cushion of claim 58 wherein the backing layer is translucent.60. The adhesive cushion of claim 54 having a skin-contacting area inthe range of about 3-250 cm².
 61. The adhesive cushion of claim 54 whichcomprises about 10-50 wt % hydrophobic polymer; about 5-40 wt %elastomeric plasticizer; about 0.5-40 wt % tackifying resin; about 5-40wt % high molecular weight cellulose derived polymers; about 2-30 wt %reinforcing clay particles; and about 0-20 wt % optional ingredients.62. The adhesive cushion of claim 61 which comprises about 2-40 wt %naturally occurring polysaccharides.
 63. The adhesive cushion of claim61 which comprises about 1-20 wt % low molecular weight cellulosederived polymers.
 64. The adhesive cushion of claim 54 wherein thehydrophobic polymer is selected from the group consisting of butadieneacrylonitrile rubber, butyl rubbers, ethylene-propylene-dieneterpolymers, isobutylene-isoprene copolymers, natural rubber adhesives,polychloroprenes, polyisobutylenes, polyisoprenes, polysiloxanes,styrene-butadiene-styrene block copolymers, styrene-isoprene-styreneblock copolymers, vinyl ether polymers, and combinations thereof. 65.The adhesive cushion of claim 54 wherein the hydrophobic polymer isselected from the group consisting of butyl rubbers, polyisoprenes,styrene-butadiene-styrene block copolymers, styrene-isoprene-styreneblock copolymers, and combinations thereof.
 66. The adhesive cushion ofclaim 54 wherein the high molecular weight cellulose derived polymer isselected from the group consisting of hydroxypropylcellulose,hydroxypropylmethylcellulose, sodium carboxymethylcellulose, andcombinations thereof.
 67. The adhesive cushion of claim 66 wherein thehigh molecular weight cellulose derived polymers have a molecular weightwithin the range of about 300-1,150 kg/mole.
 68. The adhesive cushion ofclaim 54 wherein the hydrophilic phase comprises at least one naturallyoccurring polysaccharide selected from the group consisting of agars,alginates, carrageenans, chitin, chitosan, glucomannan, gum guar, gellangum, locust bean gum, pectins, pullulan, starches and xanthans, andcombinations thereof.
 69. The adhesive cushion of claim 54 wherein thehydrophilic phase comprises at least one low molecular weight cellulosederived polymer selected from the group consisting ofhydroxypropylcellulose, hydroxypropylmethylcellulose, sodiumcarboxymethylcellulose, and combinations thereof.
 70. The adhesivecushion of claim 69 wherein the low molecular weight cellulose derivedpolymers have a molecular weight within the range of about 80-140kg/mole.
 71. The adhesive cushion of claim 54 wherein the clay particlesare comprised of montmorillonite.
 72. The adhesive cushion of claim 54wherein the hydrophobic phase comprises a styrene-isoprene-styrene blockcopolymer in combination with a styrene-isoprene block copolymer, a lowmolecular weight polyisoprene rubber and a non-polar tackifying resin;and the hydrophilic phase comprises agar, high molecular weighthydroxypropylcellulose and reinforced clay particles.
 73. The adhesivecushion of claim 72 which further comprises a polyisobutylene adhesivematerial.
 74. The adhesive cushion of claim 54 wherein the hydrophobicphase comprises a styrene-isoprene-styrene block copolymer incombination with a styrene-isoprene block copolymer, a low molecularweight polyisoprene rubber and a non-polar tackifying resin; and thehydrophilic phase comprises low molecular weight hydroxypropylcellulose,agar, high molecular weight hydroxypropylcellulose and reinforced clayparticles.
 75. The adhesive cushion of claim 74 which further comprisesa polyisobutylene adhesive material.
 76. A wound dressing comprising alaminated composite of a body facing layer having a body-contactingsurface, and an outwardly facing non-occlusive backing layer, wherein atleast a portion of the body-contacting surface is comprised of askin-contacting adhesive comprised of a hydrophobic phase and ahydrophilic phase, wherein: (a) the hydrophobic phase comprises ahydrophobic polymer, at least one elastomeric plasticizer and atackifying resin; and (b) the hydrophilic phase comprises: i) at leastone material selected from the group consisting of low molecular weightcellulose derived polymers and naturally occurring polysaccharides; ii)at least one high molecular weight cellulose derived polymer; and iii)reinforcing clay particles.
 77. The wound dressing of claim 76 whichfurther includes a backing layer.
 78. The wound dressing of claim 76which further includes a removable release liner covering andco-extensive with the body-facing surface.
 79. The wound dressing ofclaim 76 which further comprises a therapeutically effective amount ofan active agent suitable for application to a wound.
 80. The wounddressing of claim 76 which comprises about 10-50 wt % hydrophobicpolymer; about 5-40 wt % elastomeric plasticizer; about 0.5-40 wt %tackifying resin; about 5-40 wt % high molecular weight cellulosederived polymers; about 2-30 wt % reinforcing clay particles; and about0-20 wt % optional ingredients.
 81. The wound dressing of claim 80 whichcomprises about 2-40 wt % naturally occurring polysaccharides.
 82. Thewound dressing of claim 80 which comprises about 1-20 wt % low molecularweight cellulose derived polymers.
 83. The wound dressing of claim 76wherein the hydrophobic polymer is selected from the group consisting ofbutadiene acrylonitrile rubber, butyl rubbers, ethylene-propylene-dieneterpolymers, isobutylene-isoprene copolymers, natural rubber adhesives,polychloroprenes, polyisobutylenes, polyisoprenes, polysiloxanes,styrene-butadiene-styrene block copolymers, styrene-isoprene-styreneblock copolymers, vinyl ether polymers, and combinations thereof. 84.The wound dressing of claim 76 wherein the high molecular weightcellulose derived polymers are selected from the group consisting ofhydroxypropylcellulose, hydroxypropylmethylcellulose and sodiumcarboxymethylcellulose.
 85. The wound dressing of claim 84 wherein thehydrophilic phase comprises at least one low molecular weight cellulosederived polymer selected from the group consisting ofhydroxypropylcellulose, hydroxypropylmethylcellulose and sodiumcarboxymethylcellulose.
 86. The wound dressing of claim 84 wherein thehydrophilic phase comprises at least one naturally occurringpolysaccharide selected from the group consisting of agars, alginates,carrageenans, chitin, chitosan, glucomannan, gum guar, gellan gum,locust bean gum, pectins, pullulan, starches and xanthans, andcombinations thereof.
 87. The wound dressing of claim 76 wherein theclay particles are comprised of montmorillonite.
 88. The wound dressingof claim 76 wherein the hydrophobic phase comprises astyrene-isoprene-styrene block copolymer in combination with astyrene-isoprene block copolymer, a low molecular weight polyisoprenerubber and a non-polar tackifying resin; and the hydrophilic phasecomprises low molecular weight hydroxypropylcellulose, high molecularweight hydroxypropylcellulose and reinforced clay particles.
 89. Thewound dressing of claim 88 which further comprises a polyisobutyleneadhesive material.
 90. A transdermal drug delivery device comprised of adrug reservoir containing a therapeutically effective amount of anactive agent, an outwardly facing backing layer, and a means foraffixing the device to a body surface comprising a skin-contactingadhesive composition, wherein the adhesive composition comprises: (a) ahydrophobic phase comprising a hydrophobic polymer, at least oneelastomeric plasticizer and a tackifying resin; and (b) a hydrophilicphase comprising: i) at least one material selected from the groupconsisting of low molecular weight cellulose derived polymers andnaturally occurring polysaccharides; ii) at least one high molecularweight cellulose derived polymer; and iii) reinforcing clay particles.91. The transdermal drug delivery device of claim 90 wherein thehydrophobic polymer is selected from the group consisting of butadieneacrylonitrile rubber, butyl rubbers, ethylene-propylene-dieneterpolymers, isobutylene-isoprene copolymers, natural rubber adhesives,polychloroprenes, polyisobutylenes, polyisoprenes, polysiloxanes,styrene-butadiene-styrene block copolymers, styrene-isoprene-styreneblock copolymers, vinyl ether polymers, and combinations thereof. 92.The transdermal drug delivery device of claim 90 wherein the highmolecular weight cellulose derived polymers are selected from the groupconsisting of hydroxypropylcellulose, hydroxypropylmethylcellulose andsodium carboxymethylcellulose.
 93. The transdermal drug delivery deviceof claim 90 wherein the hydrophilic phase comprises at least one lowmolecular weight cellulose derived polymer selected from the groupconsisting of hydroxypropylcellulose, hydroxypropylmethylcellulose andsodium carboxymethylcellulose.
 94. The transdermal drug delivery deviceof claim 90 wherein the hydrophilic phase comprises at least onenaturally occurring polysaccharide selected from the group consisting ofagars, alginates, carrageenans, chitin, chitosan, glucomannan, gum guar,gellan gum, locust bean gum, pectins, pullulan, starches and xanthans,and combinations thereof.
 95. The transdermal drug delivery device ofclaim 90 wherein the clay particles are comprised of montmorillonite.96. The transdermal drug delivery device of claim 90 wherein theskin-contacting adhesive composition is separate from the drugreservoir.
 97. The transdermal drug delivery device of claim 90 whereinthe skin-contacting adhesive composition serves as the drug reservoir.98. The transdermal drug delivery device of claim 90 which furthercomprises a rate controlling membrane.
 99. A skin-contacting adhesivecomposition comprised of a hydrophobic phase and a hydrophilic phase,wherein the hydrophilic phase comprises: i) randomly distributedspherical solid droplets comprised of a material selected from the groupof low molecular weight cellulose derived polymers, naturally occurringpolysaccharides, and combinations thereof; ii) fibers comprised of aliquid crystalline high molecular weight cellulose derived polymer; andiii) ordered particles comprised of clay.